Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans.

PubMed

Fresnay, Stephanie; McArthur, Monica A; Magder, Laurence; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

2016-03-01

Typhoid fever, caused by the human-restricted organism Salmonella Typhi (S. Typhi), is a major public health problem worldwide. Development of novel vaccines remains imperative, but is hampered by an incomplete understanding of the immune responses that correlate with protection. Recently, a controlled human infection model was re-established in which volunteers received ~10(3) cfu wild-type S. Typhi (Quailes strain) orally. Twenty-one volunteers were evaluated for their cell-mediated immune (CMI) responses. Ex vivo PBMC isolated before and up to 1 year after challenge were exposed to three S. Typhi-infected targets, i.e., autologous B lymphoblastoid cell-lines (B-LCL), autologous blasts and HLA-E restricted AEH B-LCL cells. CMI responses were evaluated using 14-color multiparametric flow cytometry to detect simultaneously five intracellular cytokines/chemokines (i.e., IL-17A, IL-2, IFN-g, TNF-a and MIP-1b) and a marker of degranulation/cytotoxic activity (CD107a). Herein we provide the first evidence that S. Typhi-specific CD8+ responses correlate with clinical outcome in humans challenged with wild-type S. Typhi. Higher multifunctional S. Typhi-specific CD8+ baseline responses were associated with protection against typhoid and delayed disease onset. Moreover, following challenge, development of typhoid fever was accompanied by decreases in circulating S. Typhi-specific CD8+ T effector/memory (TEM) with gut homing potential, suggesting migration to the site(s) of infection. In contrast, protection against disease was associated with low or no changes in circulating S. Typhi-specific TEM. These studies provide novel insights into the protective immune responses against typhoid disease that will aid in selection and development of new vaccine candidates.

Novel Structure and Function of Typhoid Toxin

MedlinePlus

... the reasons why Salmonella typhi , the cause of typhoid fever, is so dangerous. The findings could help guide ... A few people, known as carriers, recover from typhoid fever but continue to carry the bacteria. Perhaps the ...

Whole Genome Sequence Analysis of Salmonella Typhi Isolated in Thailand before and after the Introduction of a National Immunization Program

PubMed Central

Thanh, Duy Pham; Bodhidatta, Ladaporn; Mason, Carl Jeffries; Srijan, Apichai; Rabaa, Maia A.; Vinh, Phat Voong; Thanh, Tuyen Ha; Thwaites, Guy E.; Baker, Stephen; Holt, Kathryn E.

2017-01-01

Vaccines against Salmonella Typhi, the causative agent of typhoid fever, are commonly used by travellers, however, there are few examples of national immunization programs in endemic areas. There is therefore a paucity of data on the impact of typhoid immunization programs on localised populations of S. Typhi. Here we have used whole genome sequencing (WGS) to characterise 44 historical bacterial isolates collected before and after a national typhoid immunization program that was implemented in Thailand in 1977 in response to a large outbreak; the program was highly effective in reducing typhoid case numbers. Thai isolates were highly diverse, including 10 distinct phylogenetic lineages or genotypes. Novel prophage and plasmids were also detected, including examples that were previously only reported in Shigella sonnei and Escherichia coli. The majority of S. Typhi genotypes observed prior to the immunization program were not observed following it. Post-vaccine era isolates were more closely related to S. Typhi isolated from neighbouring countries than to earlier Thai isolates, providing no evidence for the local persistence of endemic S. Typhi following the national immunization program. Rather, later cases of typhoid appeared to be caused by the occasional importation of common genotypes from neighbouring Vietnam, Laos, and Cambodia. These data show the value of WGS in understanding the impacts of vaccination on pathogen populations and provide support for the proposal that large-scale typhoid immunization programs in endemic areas could result in lasting local disease elimination, although larger prospective studies are needed to test this directly. PMID:28060810

Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

PubMed

Hannemann, Sebastian; Galán, Jorge E

2017-07-01

Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

A large outbreak of typhoid fever associated with a high rate of intestinal perforation in Kasese District, Uganda, 2008-2009.

PubMed

Neil, Karen P; Sodha, Samir V; Lukwago, Luswa; O-Tipo, Shikanga; Mikoleit, Matthew; Simington, Sherricka D; Mukobi, Peter; Balinandi, Stephen; Majalija, Samuel; Ayers, Joseph; Kagirita, Atek; Wefula, Edward; Asiimwe, Frank; Kweyamba, Vianney; Talkington, Deborah; Shieh, Wun-Ju; Adem, Patricia; Batten, Brigid C; Zaki, Sherif R; Mintz, Eric

2012-04-01

Salmonella enterica serovar Typhi (Salmonella Typhi) causes an estimated 22 million typhoid fever cases and 216 000 deaths annually worldwide. In Africa, the lack of laboratory diagnostic capacity limits the ability to recognize endemic typhoid fever and to detect outbreaks. We report a large laboratory-confirmed outbreak of typhoid fever in Uganda with a high proportion of intestinal perforations (IPs). A suspected case of typhoid fever was defined as fever and abdominal pain in a person with either vomiting, diarrhea, constipation, headache, weakness, arthralgia, poor response to antimalarial medications, or IP. From March 4, 2009 to April 17, 2009, specimens for blood and stool cultures and serology were collected from suspected cases. Antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) were performed on Salmonella Typhi isolates. Surgical specimens from patients with IP were examined. A community survey was conducted to characterize the extent of the outbreak. From December 27, 2007 to July 30, 2009, 577 cases, 289 hospitalizations, 249 IPs, and 47 deaths from typhoid fever occurred; Salmonella Typhi was isolated from 27 (33%) of 81 patients. Isolates demonstrated multiple PFGE patterns and uniform susceptibility to ciprofloxacin. Surgical specimens from 30 patients were consistent with typhoid fever. Estimated typhoid fever incidence in the community survey was 8092 cases per 100 000 persons. This typhoid fever outbreak was detected because of an elevated number of IPs. Underreporting of milder illnesses and delayed and inadequate antimicrobial treatment contributed to the high perforation rate. Enhancing laboratory capacity for detection is critical to improving typhoid fever control.

A mouse model of Salmonella typhi infection

PubMed Central

Mathur, Ramkumar; Oh, Hyunju; Zhang, Dekai; Park, Sung-Gyoo; Seo, Jin; Koblansky, Alicia; Hayden, Matthew S.; Ghosh, Sankar

2012-01-01

Salmonella spp. are gram-negative flagellated bacteria that can cause food and water-borne gastroenteritis and typhoid fever in humans. We now report that flagellin from Salmonella spp. is recognized in mouse intestine by Toll-like receptor 11 (TLR11). Absence of TLR11 renders mice more susceptible to infection by S. typhimurium, with increased dissemination of the bacteria and enhanced lethality. Unlike S. typhimurium, S. typhi, a human obligatory pathogen that causes typhoid fever, is normally unable to infect mice. TLR11 is expressed in mice but not in humans, and remarkably, we find that tlr11−/− mice are efficiently infected with orally-administered S. typhi. We also find that tlr11−/− mice can be immunized against S. typhi. Therefore, tlr11−/− mice represent the first small animal model for the study of the immune response to S. typhi, and for the development of vaccines against this important human pathogen. PMID:23101627

Early diagnosis of typhoid fever by nested PCR for flagellin gene of Salmonella enterica serotype Typhi.

PubMed

Khan, S; Harish, B N; Menezes, G A; Acharya, N S; Parija, S C

2012-11-01

Typhoid fever caused by Salmonella Typhi continues to be a major health problem in spite of the use of antibiotics and the development of newer antibacterial drugs. Inability to make an early laboratory diagnosis and resort to empirical therapy, often lead to increased morbidity and mortality in cases of typhoid fever. This study was aimed to optimize a nested PCR for early diagnosis of typhoid fever and using it as a diagnostic tool in culture negative cases of suspected typhoid fever. Eighty patients with clinical diagnosis of typhoid fever and 40 controls were included in the study. The blood samples collected were subjected to culture, Widal and nested PCR targeting the flagellin gene of S. Typhi. The sensitivity of PCR on blood was found to be 100 per cent whereas the specificity was 76.9 per cent. The positive predictive value (PPV) of PCR was calculated to be 76.9 per cent with an accuracy of 86 per cent. None of the 40 control samples gave a positive PCR. Due to its high sensitivity and specificity nested PCR can be used as a useful tool to diagnose clinically suspected, culture negative cases of typhoid fever.

Temporal Fluctuation of Multidrug Resistant Salmonella Typhi Haplotypes in the Mekong River Delta Region of Vietnam

PubMed Central

Chau, Tran Thuy; Duy, Pham Thanh; La, Tran Thi Phi; Hoang, Nguyen Van Minh; Nga, Tran Vu Thieu; Campbell, James I.; Manh, Bui Huu; Vinh Chau, Nguyen Van; Hien, Tran Tinh; Farrar, Jeremy; Dougan, Gordon; Baker, Stephen

2011-01-01

Background Typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. Principal Findings The population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. Significance The H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam. PMID:21245916

Rapid and Sensitive Salmonella Typhi Detection in Blood and Fecal Samples Using Reverse Transcription Loop-Mediated Isothermal Amplification.

PubMed

Fan, Fenxia; Yan, Meiying; Du, Pengcheng; Chen, Chen; Kan, Biao

2015-09-01

Typhoid fever caused by Salmonella enterica serovar Typhi remains a significant public health problem in developing countries. Although the main method for diagnosing typhoid fever is blood culture, the test is time consuming and not always able to detect infections. Thus, it is very difficult to distinguish typhoid from other infections in patients with nonspecific symptoms. A simple and sensitive laboratory detection method remains necessary. The purpose of this study is to establish and evaluate a rapid and sensitive reverse transcription-based loop-mediated isothermal amplification (RT-LAMP) method to detect Salmonella Typhi infection. In this study, a new specific gene marker, STY1607, was selected to develop a STY1607-RT-LAMP assay; this is the first report of specific RT-LAMP detection assay for typhoid. Human-simulated and clinical blood/stool samples were used to evaluate the performance of STY1607-RT-LAMP for RNA detection; this method was compared with STY1607-LAMP, reverse transcription real-time polymerase chain reaction (rRT-PCR), and bacterial culture methods for Salmonella Typhi detection. Using mRNA as the template, STY1607-RT-LAMP exhibited 50-fold greater sensitivity than STY1607-LAMP for DNA detection. The STY1607-RT-LAMP detection limit is 3 colony-forming units (CFU)/mL for both the pure Salmonella Typhi samples and Salmonella Typhi-simulated blood samples and was 30 CFU/g for the simulated stool samples, all of which were 10-fold more sensitive than the rRT-PCR method. RT-LAMP exhibited improved Salmonella Typhi detection sensitivity compared to culture methods and to rRT-PCR of clinical blood and stool specimens from suspected typhoid fever patients. Because it can be performed without sophisticated equipment or skilled personnel, RT-LAMP is a valuable tool for clinical laboratories in developing countries. This method can be applied in the clinical diagnosis and care of typhoid fever patients as well as for a quick public health response.

Serum bactericidal assay for the evaluation of typhoid vaccine using a semi-automated colony-counting method.

PubMed

Jang, Mi Seon; Sahastrabuddhe, Sushant; Yun, Cheol-Heui; Han, Seung Hyun; Yang, Jae Seung

2016-08-01

Typhoid fever, mainly caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening disease, mostly in developing countries. Enzyme-linked immunosorbent assay (ELISA) is widely used to quantify antibodies against S. Typhi in serum but does not provide information about functional antibody titers. Although the serum bactericidal assay (SBA) using an agar plate is often used to measure functional antibody titers against various bacterial pathogens in clinical specimens, it has rarely been used for typhoid vaccines because it is time-consuming and labor-intensive. In the present study, we established an improved SBA against S. Typhi using a semi-automated colony-counting system with a square agar plate harboring 24 samples. The semi-automated SBA efficiently measured bactericidal titers of sera from individuals immunized with S. Typhi Vi polysaccharide vaccines. The assay specifically responded to S. Typhi Ty2 but not to other irrelevant enteric bacteria including Vibrio cholerae and Shigella flexneri. Baby rabbit complement was more appropriate source for the SBA against S. Typhi than complements from adult rabbit, guinea pig, and human. We also examined the correlation between SBA and ELISA for measuring antibody responses against S. Typhi using pre- and post-vaccination sera from 18 human volunteers. The SBA titer showed a good correlation with anti-Vi IgG quantity in the serum as determined by Spearman correlation coefficient of 0.737 (P < 0.001). Taken together, the semi-automated SBA might be efficient, accurate, sensitive, and specific enough to measure functional antibody titers against S. Typhi in sera from human subjects immunized with typhoid vaccines. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins.

PubMed

Klemm, Elizabeth J; Shakoor, Sadia; Page, Andrew J; Qamar, Farah Naz; Judge, Kim; Saeed, Dania K; Wong, Vanessa K; Dallman, Timothy J; Nair, Satheesh; Baker, Stephen; Shaheen, Ghazala; Qureshi, Shahida; Yousafzai, Mohammad Tahir; Saleem, Muhammad Khalid; Hasan, Zahra; Dougan, Gordon; Hasan, Rumina

2018-02-20

Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S  Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S  Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the bla CTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S  Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally. IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S  Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S  Typhi clone in Sindh, Pakistan. The XDR S  Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S  Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S  Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S  Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S  Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S  Typhi observed here adds urgency to the need for typhoid prevention measures. Copyright © 2018 Klemm et al.

Salmonella Infections (For Parents)

MedlinePlus

... iguanas). Another, rarer form — called Salmonella typhi — causes typhoid fever . What Is Salmonella Infection? Salmonella infection, or salmonellosis , ... More on this topic for: Parents Kids Teens Typhoid Fever E. Coli Stool Test: Bacteria Culture Food Safety ...

The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.

PubMed

Pham Thanh, Duy; Thompson, Corinne N; Rabaa, Maia A; Sona, Soeng; Sopheary, Sun; Kumar, Varun; Moore, Catrin; Tran Vu Thieu, Nga; Wijedoru, Lalith; Holt, Kathryn E; Wong, Vanessa; Pickard, Derek; Thwaites, Guy E; Day, Nicholas; Dougan, Gordon; Turner, Paul; Parry, Christopher M; Baker, Stephen

2016-06-01

Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC) in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS) on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1-11.5 years). The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged <15 years were observed over the study period. A population-based risk factor analysis found that access to water within households and increasing distance from Tonle Sap Lake were protective. Spatial mapping and WGS provided additional resolution for these findings, and confirmed that proximity to the lake was associated with discrete spatiotemporal disease clusters. We confirmed the dominance of MDR H58 S. Typhi in this population, and found substantial evidence of diversification (at least seven sublineages) within this single lineage. We conclude that there is a substantial burden of pediatric typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines.

The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia

PubMed Central

Rabaa, Maia A; Sona, Soeng; Sopheary, Sun; Kumar, Varun; Moore, Catrin; Tran Vu Thieu, Nga; Wijedoru, Lalith; Holt, Kathryn E.; Wong, Vanessa; Pickard, Derek; Thwaites, Guy E.; Day, Nicholas; Dougan, Gordon; Turner, Paul; Parry, Christopher M.; Baker, Stephen

2016-01-01

Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC) in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS) on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1–11.5 years). The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged <15 years were observed over the study period. A population-based risk factor analysis found that access to water within households and increasing distance from Tonle Sap Lake were protective. Spatial mapping and WGS provided additional resolution for these findings, and confirmed that proximity to the lake was associated with discrete spatiotemporal disease clusters. We confirmed the dominance of MDR H58 S. Typhi in this population, and found substantial evidence of diversification (at least seven sublineages) within this single lineage. We conclude that there is a substantial burden of pediatric typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines. PMID:27331909

Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies.

PubMed

Waddington, Claire S; Darton, Thomas C; Woodward, William E; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2014-05-01

Typhoid infection causes considerable morbidity and mortality worldwide, particularly in settings where lack of clean water and inadequate sanitation facilitate disease spread through faecal-oral transmission. Improved understanding of the pathogenesis, immune control and microbiology of Salmonella Typhi infection can help accelerate the development of improved vaccines and diagnostic tests necessary for disease control. S. Typhi is a human-restricted pathogen; therefore animal models are limited in their relevance to human infection. During the latter half of the 20th century, induced human infection ("challenge") studies with S. Typhi were used effectively to assess quantitatively the human host response to challenge and to measure directly the efficacy of typhoid vaccines in preventing clinical illness. Here, the findings of these historic challenge studies are reviewed, highlighting the pivotal role that challenge studies have had in improving our understanding of the host-pathogen interaction, and illustrating issues relevant to modern typhoid challenge model design. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Dynamic Modularity of Host Protein Interaction Networks in Salmonella Typhi Infection

PubMed Central

Dhal, Paltu Kumar; Barman, Ranjan Kumar; Saha, Sudipto; Das, Santasabuj

2014-01-01

Background Salmonella Typhi is a human-restricted pathogen, which causes typhoid fever and remains a global health problem in the developing countries. Although previously reported host expression datasets had identified putative biomarkers and therapeutic targets of typhoid fever, the underlying molecular mechanism of pathogenesis remains incompletely understood. Methods We used five gene expression datasets of human peripheral blood from patients suffering from S. Typhi or other bacteremic infections or non-infectious disease like leukemia. The expression datasets were merged into human protein interaction network (PIN) and the expression correlation between the hubs and their interacting proteins was measured by calculating Pearson Correlation Coefficient (PCC) values. The differences in the average PCC for each hub between the disease states and their respective controls were calculated for studied datasets. The individual hubs and their interactors with expression, PCC and average PCC values were treated as dynamic subnetworks. The hubs that showed unique trends of alterations specific to S. Typhi infection were identified. Results We identified S. Typhi infection-specific dynamic subnetworks of the host, which involve 81 hubs and 1343 interactions. The major enriched GO biological process terms in the identified subnetworks were regulation of apoptosis and biological adhesions, while the enriched pathways include cytokine signalling in the immune system and downstream TCR signalling. The dynamic nature of the hubs CCR1, IRS2 and PRKCA with their interactors was studied in detail. The difference in the dynamics of the subnetworks specific to S. Typhi infection suggests a potential molecular model of typhoid fever. Conclusions Hubs and their interactors of the S. Typhi infection-specific dynamic subnetworks carrying distinct PCC values compared with the non-typhoid and other disease conditions reveal new insight into the pathogenesis of S. Typhi. PMID:25144185

Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer

PubMed Central

Cavallo, Ilaria; Pontone, Martina; Toma, Luigi; Ensoli, Fabrizio

2017-01-01

Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention. PMID:28858232

An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid

PubMed Central

Wong, Vanessa K.; Baker, Stephen; Connor, Thomas R.; Pickard, Derek; Page, Andrew J.; Dave, Jayshree; Murphy, Niamh; Holliman, Richard; Sefton, Armine; Millar, Michael; Dyson, Zoe A.; Dougan, Gordon; Holt, Kathryn E.; Parkhill, Julian; Feasey, Nicholas A.; Kingsley, Robert A.; Thomson, Nicholas R.; Keane, Jacqueline A.; Weill, François- Xavier; Le Hello, Simon; Hawkey, Jane; Edwards, David J.; Harris, Simon R.; Cain, Amy K.; Hadfield, James; Hart, Peter J.; Thieu, Nga Tran Vu; Klemm, Elizabeth J.; Breiman, Robert F.; Watson, Conall H.; Edmunds, W. John; Kariuki, Samuel; Gordon, Melita A.; Heyderman, Robert S.; Okoro, Chinyere; Jacobs, Jan; Lunguya, Octavie; Msefula, Chisomo; Chabalgoity, Jose A.; Kama, Mike; Jenkins, Kylie; Dutta, Shanta; Marks, Florian; Campos, Josefina; Thompson, Corinne; Obaro, Stephen; MacLennan, Calman A.; Dolecek, Christiane; Keddy, Karen H.; Smith, Anthony M.; Parry, Christopher M.; Karkey, Abhilasha; Dongol, Sabina; Basnyat, Buddha; Arjyal, Amit; Mulholland, E. Kim; Campbell, James I.; Dufour, Muriel; Bandaranayake, Don; Toleafoa, Take N.; Singh, Shalini Pravin; Hatta, Mochammad; Newton, Paul N.; Dance, David; Davong, Viengmon; Onsare, Robert S.; Isaia, Lupeoletalalelei; Thwaites, Guy; Wijedoru, Lalith; Crump, John A.; De Pinna, Elizabeth; Nair, Satheesh; Nilles, Eric J.; Thanh, Duy Pham; Turner, Paul; Soeng, Sona; Valcanis, Mary; Powling, Joan; Dimovski, Karolina; Hogg, Geoff; Farrar, Jeremy; Mather, Alison E.; Amos, Ben

2016-01-01

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations. PMID:27703135

Epidemic typhoid in Chile: analysis by molecular and conventional methods of Salmonella typhi strain diversity in epidemic (1977 and 1981) and nonepidemic (1990) years.

PubMed

Fica, A E; Prat-Miranda, S; Fernandez-Ricci, A; D'Ottone, K; Cabello, F C

1996-07-01

From 1977 to 1986, Chile experienced an important typhoid fever epidemic, despite statistics that indicated apparently improving levels of sanitation of drinking water and sewage disposal. The lack of antibiotic resistance among the Salmonella typhi strains isolated during this period, the mild clinical presentation of the disease, and the initially low level of efficacy of the S. typhi Ty21a vaccine in the population exposed to the epidemic suggested that this epidemic might have resulted from the dissemination of S. typhi strains with unique characteristics. To investigate this hypothesis, we used conventional methods (bacteriophage typing and biotyping) and molecular methods (restriction fragment length polymorphism analysis, ribotyping, IS200 typing, and PCR amplification of the fliC-d gene) to study a population of 149 S. typhi isolates during 1977, 1981, and 1990, the years that included periods with low (when the disease was endemic) and high (when the disease was epidemic) morbidities. Our results indicate that these S. typhi isolates in Chile represent a number of highly diverse variants of the clone of S. typhi with a worldwide distribution described by Selander et al. (R. K. Selander, P. Beltran, N.H. Smith, R. Helmuth, F.A. Rubin, D.J. Kopecko, K. Ferris, B.D. Tall, A. Cravioto, and J.M. Musser, Infect. Immun. 58:2262-2275, 1990). For example, we detected 26 PstI and 10 ClaI ribotypes among 47 and 16 S. typhi strains belonging to this clone, respectively. These results suggest that the Chilean epidemic was probably produced by multiple sources of infection because of deficient sanitary conditions. These findings illustrate the usefulness of molecular methods for characterizing the potential causes of the typhoid epidemics and the possible routes of transmission of S. typhi strains in typhoid epidemics.

Epidemic typhoid in Chile: analysis by molecular and conventional methods of Salmonella typhi strain diversity in epidemic (1977 and 1981) and nonepidemic (1990) years.

PubMed Central

Fica, A E; Prat-Miranda, S; Fernandez-Ricci, A; D'Ottone, K; Cabello, F C

1996-01-01

From 1977 to 1986, Chile experienced an important typhoid fever epidemic, despite statistics that indicated apparently improving levels of sanitation of drinking water and sewage disposal. The lack of antibiotic resistance among the Salmonella typhi strains isolated during this period, the mild clinical presentation of the disease, and the initially low level of efficacy of the S. typhi Ty21a vaccine in the population exposed to the epidemic suggested that this epidemic might have resulted from the dissemination of S. typhi strains with unique characteristics. To investigate this hypothesis, we used conventional methods (bacteriophage typing and biotyping) and molecular methods (restriction fragment length polymorphism analysis, ribotyping, IS200 typing, and PCR amplification of the fliC-d gene) to study a population of 149 S. typhi isolates during 1977, 1981, and 1990, the years that included periods with low (when the disease was endemic) and high (when the disease was epidemic) morbidities. Our results indicate that these S. typhi isolates in Chile represent a number of highly diverse variants of the clone of S. typhi with a worldwide distribution described by Selander et al. (R. K. Selander, P. Beltran, N.H. Smith, R. Helmuth, F.A. Rubin, D.J. Kopecko, K. Ferris, B.D. Tall, A. Cravioto, and J.M. Musser, Infect. Immun. 58:2262-2275, 1990). For example, we detected 26 PstI and 10 ClaI ribotypes among 47 and 16 S. typhi strains belonging to this clone, respectively. These results suggest that the Chilean epidemic was probably produced by multiple sources of infection because of deficient sanitary conditions. These findings illustrate the usefulness of molecular methods for characterizing the potential causes of the typhoid epidemics and the possible routes of transmission of S. typhi strains in typhoid epidemics. PMID:8784573

ESBL-Producing Salmonella enterica Serovar Typhi in Traveler Returning from Guatemala to Spain

PubMed Central

Piedra-Carrasco, Nuria; Salvador, Fernando; Rodríguez, Virginia; Sánchez-Montalvá, Adrián; Planes, Anna M.; Molina, Israel; Larrosa, M. Nieves

2014-01-01

We report a case of typhoid fever in a traveler returning to Spain from Guatemala that was caused by Salmonella enterica serovar Typhi which produced an extended-spectrum β-lactamase (ESBL). This finding demonstrates the presence of ESBL-producing S. enterica ser. Typhi strains in the Americas. Enhanced surveillance is necessary to prevent further spread. PMID:25340972

Conferring Virulence: Structure and Function of the chimeric A2B5 Typhoid Toxin

PubMed Central

Song, Jeongmin; Gao, Xiang; Galán, Jorge E.

2013-01-01

Salmonella Typhi differs from most other salmonellae in that it causes a life-threatening systemic infection known as typhoid fever1. The molecular bases for its unique clinical presentation are unknown2. Here we found that in an animal model, the systemic administration of typhoid toxin, a unique virulence factor of S. Typhi, reproduces many of the acute symptoms of typhoid fever. We identified specific carbohydrate moieties on specific surface glycoproteins that serve as receptors for typhoid toxin, which explains its broad cell target specificity. We present the atomic structure of typhoid toxin, which shows an unprecedented A2B5 organization with two covalently-linked A subunits non-covalently-associated to a pentameric B subunit. The structure provides insight into the toxin’s receptor-binding specificity and delivery mechanisms and reveals how the activities of two powerful toxins have been coopted into a single, unique toxin that can induce many of the symptoms characteristic of typhoid fever. These findings may lead to the development of potentially life-saving therapeutics against typhoid fever. PMID:23842500

Emerging insights into the biology of typhoid toxin

PubMed Central

Fowler, Casey C.; Chang, Shu-Jung; Gao, Xiang; Geiger, Tobias; Stack, Gabrielle; Galán, Jorge E.

2017-01-01

Typhoid toxin is a unique A2B5 exotoxin and an important virulence factor for Salmonella Typhi, the cause of typhoid fever. In the decade since its initial discovery, great strides have been made in deciphering the unusual biological program of this toxin, which is fundamentally different from related toxins in many ways. Purified typhoid toxin administered to laboratory animals causes many of the symptoms of typhoid fever, suggesting that typhoid toxin is a central factor in this disease. Further advances in understanding the biology of this toxin will help guide the development of badly needed diagnostics and therapeutic interventions that target this toxin to detect, prevent or treat typhoid fever. PMID:28213043

Comparison of Salmonella enterica Serovars Typhi and Typhimurium Reveals Typhoidal Serovar-Specific Responses to Bile

PubMed Central

Johnson, Rebecca; Ravenhall, Matt; Pickard, Derek; Dougan, Gordon; Byrne, Alexander

2017-01-01

ABSTRACT Salmonella enterica serovars Typhi and Typhimurium cause typhoid fever and gastroenteritis, respectively. A unique feature of typhoid infection is asymptomatic carriage within the gallbladder, which is linked with S. Typhi transmission. Despite this, S. Typhi responses to bile have been poorly studied. Transcriptome sequencing (RNA-Seq) of S. Typhi Ty2 and a clinical S. Typhi isolate belonging to the globally dominant H58 lineage (strain 129-0238), as well as S. Typhimurium 14028, revealed that 249, 389, and 453 genes, respectively, were differentially expressed in the presence of 3% bile compared to control cultures lacking bile. fad genes, the actP-acs operon, and putative sialic acid uptake and metabolism genes (t1787 to t1790) were upregulated in all strains following bile exposure, which may represent adaptation to the small intestine environment. Genes within the Salmonella pathogenicity island 1 (SPI-1), those encoding a type IIII secretion system (T3SS), and motility genes were significantly upregulated in both S. Typhi strains in bile but downregulated in S. Typhimurium. Western blots of the SPI-1 proteins SipC, SipD, SopB, and SopE validated the gene expression data. Consistent with this, bile significantly increased S. Typhi HeLa cell invasion, while S. Typhimurium invasion was significantly repressed. Protein stability assays demonstrated that in S. Typhi the half-life of HilD, the dominant regulator of SPI-1, is three times longer in the presence of bile; this increase in stability was independent of the acetyltransferase Pat. Overall, we found that S. Typhi exhibits a specific response to bile, especially with regard to virulence gene expression, which could impact pathogenesis and transmission. PMID:29229736

Septic arthritis of the hip in a Cambodian child caused by multidrug-resistant Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin treated with ceftriaxone and azithromycin.

PubMed

Pocock, J M; Khun, P A; Moore, C E; Vuthy, S; Stoesser, N; Parry, C M

2014-08-01

Septic arthritis is a rare complication of typhoid fever. A 12-year-old boy without pre-existing disease attended a paediatric hospital in Cambodia with fever and left hip pain. A hip synovial fluid aspirate grew multidrug-resistant Salmonella enterica ser. Typhi with intermediate susceptibility to ciprofloxacin. Arthrotomy, 2 weeks of intravenous ceftriaxone and 4 weeks of oral azithromycin led to resolution of symptoms. The optimum management of septic arthritis in drug-resistant typhoid is undefined.

Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays.

PubMed

Goay, Yuan Xin; Chin, Kai Ling; Tan, Clarissa Ling Ling; Yeoh, Chiann Ying; Ja'afar, Ja'afar Nuhu; Zaidah, Abdul Rahman; Chinni, Suresh Venkata; Phua, Kia Kien

2016-01-01

Salmonella Typhi ( S . Typhi) causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S . Typhi with other enteric pathogens was performed, and 6 S . Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico . Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro . The diagnostic sensitivities and specificities of each assay were determined using 39 S . Typhi, 62 non-Typhi Salmonella , and 10 non- Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39) and 100% specificity (0/72). The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.

Genetic Fine Structure of a Salmonella enterica Serovar Typhi Strain Associated with the 2005 Outbreak of Typhoid Fever in Kelantan, Malaysia

PubMed Central

Baddam, Ramani; Kumar, Narender; Thong, Kwai-Lin; Ngoi, Soo-Tein; Teh, Cindy Shuan Ju; Yap, Kien-Pong; Chai, Lay-Ching; Avasthi, Tiruvayipati Suma

2012-01-01

Among enteric pathogens, Salmonella enterica serovar Typhi is responsible for the largest number of food-borne outbreaks and fatalities. The ability of the pathogen to cause systemic infection for extended durations leads to a high cost of disease control. Chronic carriers play important roles in the evolution of Salmonella Typhi; therefore, identification and in-depth characterization of isolates from clinical cases and carriers, especially those from zones of endemicity where the pathogen has not been extensively studied, are necessary. Here, we describe the genome sequence of the highly virulent Salmonella Typhi strain BL196/05 isolated during the outbreak of typhoid in Kelantan, Malaysia, in 2005. The whole-genome sequence and comparative genomics of this strain should enable us to understand the virulence mechanisms and evolutionary dynamics of this pathogen in Malaysia and elsewhere. PMID:22689247

Medical Surveillance Monthly Report. olume 22, Number 1, January 2015

DTIC Science & Technology

2015-01-01

etiologic agents for enteric fever , the prototype of which is typhoid fever caused by S. Typhi.1 In the U.S., the most common serotypes isolated in...component of the U.S. Armed Forces, Sal- monella is a leading cause of acute gastroin- testinal illness.3 Typhoid fever , in contrast, is relatively...more than 20 million cases of typhoid fever occur annually and another 5.5 million cases of enteric fever are attributed to S. Paratyphi.1 Th e most

Typhoid outbreak in Songkhla, Thailand 2009-2011: clinical outcomes, susceptibility patterns, and reliability of serology tests.

PubMed

Limpitikul, Wannee; Henpraserttae, Narong; Saksawad, Rachanee; Laoprasopwattana, Kamolwish

2014-01-01

To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi) IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009-2011 typhoid outbreak in Songkhla province in Thailand. The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin), were evaluated. S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7-14 days. The median time (IQR) of fever before treatment and duration of fever after treatment were 5 (4, 7) days and 4 (3, 5) days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%), and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively. Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.

Massive Lower Gastrointestinal Bleed caused by Typhoid Ulcer: Conservative Management.

PubMed

Goel, Apoorv; Bansal, Roli

2017-01-01

Typhoid fever is caused by gram-negative organism Salmonella typhi. The usual presentation is high-grade fever, but complications like gastrointestinal (GI) hemorrhage and perforation are also seen frequently. With the advent of antibiotics, these complications are rarely seen now. We present a case of a young female who was admitted with a diagnosis of typhoid fever presented with a massive GI bleed from ulcers in the terminal ileum and was managed conservatively without endotherapy and surgery. How to cite this article: Goel A, Bansal R. Massive Lower Gastrointestinal Bleed caused by Typhoid Ulcer: Conservative Management. Euroasian J Hepato-Gastroenterol 2017;7(2):176-177.

What Have We Learned From the Typhoid Fever Surveillance in Africa Program?

PubMed

Baker, Stephen; Hombach, Joachim; Marks, Florian

2016-03-15

The Typhoid Fever Surveillance in Africa Program (TSAP) was established in 2009 to fill the data void concerning invasive Salmonella disease in sub-Saharan Africa, and to specifically estimate the burden of bloodstream infections caused by the key pathogen, Salmonella enterica serovar Typhi. TSAP has achieved this ambitious target, finding high incidences of typhoid fever in both rural and urban populations in several countries in sub-Saharan Africa. The results of TSAP will undoubtedly dictate the direction of future typhoid fever research in Africa, and at last provides a key piece of the disease burden jigsaw puzzle. With the dawn of new Vi conjugate vaccines against Salmonella Typhi, the next priority for the typhoid community must be providing the required data on these vaccines so they can be licensed and provided to those in high-risk groups and locations across sub-Saharan Africa. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Utilization and Accessibility of Healthcare on Pemba Island, Tanzania: Implications for Health Outcomes and Disease Surveillance for Typhoid Fever

PubMed Central

Kaljee, Linda M.; Pach, Alfred; Thriemer, Kamala; Ley, Benedikt; Ali, Said M.; Jiddawi, Mohamed; Puri, Mahesh; von Seidlein, Lorenz; Deen, Jacqueline; Ochiai, Leon; Wierzba, Thomas; Clemens, John

2013-01-01

Salmonella enterica serotype Typhi (S. Typhi) was estimated to cause over 200,000 deaths and more than 21 million illnesses worldwide, including over 400,000 illnesses in Africa. The current study was conducted in four villages on Pemba Island, Zanzibar, in 2010. We present data on policy makers', health administrators', and village residents' and leaders' perceptions of typhoid fever, and hypothetical and actual health care use among village residents for typhoid fever. Qualitative data provided descriptions of home-based treatment practices and use of western pharmaceuticals, and actual healthcare use for culture-confirmed typhoid fever. Survey data indicate health facility use was associated with gender, education, residency, and perceptions of severity for symptoms associated with typhoid fever. Data have implications for education of policy makers and health administrators, design and implementation of surveillance studies, and community-based interventions to prevent disease outbreaks, decrease risks of complications, and provide information about disease recognition, diagnosis, and treatment. PMID:23208887

Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type Salmonella enterica Serovar Typhi.

PubMed

Zhang, Yan; Brady, Arthur; Jones, Cheron; Song, Yang; Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Pollard, Andrew J; Magder, Laurence S; Fasano, Alessio; Sztein, Marcelo B; Fraser, Claire M

2018-05-08

Insights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-type Salmonella enterica serovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota. Metatranscriptome analysis of longitudinal stool samples collected from study subjects revealed two stable patterns of gene expression for the human gut microbiota, dominated by transcripts from either Methanobrevibacter or a diverse representation of genera in the Firmicutes phylum. Immunization with one of two live oral attenuated vaccines against S.  Typhi had minimal effects on the composition or function of the gut microbiota. It was observed that subjects harboring the methanogen-dominated transcriptome community at baseline displayed a lower risk of developing symptoms of typhoid following challenge with wild-type S.  Typhi. Furthermore, genes encoding antioxidant proteins, metal homeostasis and transport proteins, and heat shock proteins were expressed at a higher level at baseline or after challenge with S.  Typhi in subjects who did not develop symptoms of typhoid. These data suggest that functional differences relating to redox potential and ion homeostasis in the gut microbiota may impact clinical outcomes following exposure to wild-type S.  Typhi. IMPORTANCE S.  Typhi is a significant cause of systemic febrile morbidity in settings with poor sanitation and limited access to clean water. It has been demonstrated that the human gut microbiota can influence mucosal immune responses, but there is little information available on the impact of the human gut microbiota on clinical outcomes following exposure to enteric pathogens. Here, we describe differences in the composition and function of the gut microbiota in healthy adult volunteers enrolled in a typhoid vaccine trial and report that these differences are associated with host susceptibility to or protection from typhoid after challenge with wild-type S Typhi. Our observations have important implications in interpreting the efficacy of oral attenuated vaccines against enteric pathogens in diverse populations. Copyright © 2018 Zhang et al.

Typhoid fever as a triggering factor in acute and intractable bronchial asthma attack.

PubMed

Wardhana; Surachmanto, Eko E; Datau, E A

2013-10-01

Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia, typhoid fever is endemic with high incidence of the disease. In daily practice we frequently have patients with bronchial asthma, and it is becoming worse when these patients get typhoid fever. After oral ingestion, Salmonella typhi invades the the intestine mucosa after conducted by microbial binding to epithelial cells, destroying the microfold cells (M cell) then passed through the lamina propria and detected by dendritic cells (DC) which express a variety of pathogen recognition receptors on the surfaces, including Toll-Like Receptor (TLR). expressed on macrophages and on intestinal epithelial cells inducing degradation of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process initiates the induction of pro-inflammatory gene expression profile adhesion molecules, chemokines, adhesion molecules, and other proteins that induce and perpetuate the inflammation in host cells then will induce acute ant intractable attack of bronchial asthma. The role of typhoid fever in bronchial asthma, especially in persons with acute attack of bronchial asthma, is not well understood. In this article, we will discuss the role of typhoid fever in the bronchial asthma patients which may cause bronchial asthma significantly become more severe even triggering the acute and intractable attack of bronchial asthma. This fact makes an important point, to treat completely the typhoid fever in patients with bronchial asthma.

Water-borne typhoid fever caused by an unusual Vi-phage type in Edinburgh

PubMed Central

Conn, Nancy K.; Heymann, C. S.; Jamieson, A.; McWilliam, Joan M.; Scott, T. G.

1972-01-01

Investigation of a small series of cases of typhoid fever infected in a river between 1963 and 1970 revealed that all were caused by a single source, a carrier of a rare phage type of Salmonella typhi. The contamination of the river resulted from an incorrect sewage connexion with a surface water drain outfall into the river. ImagesPlate 1 PMID:4555889

In vivo expression of Salmonella enterica serotype Typhi genes in the blood of patients with typhoid fever in Bangladesh.

PubMed

Sheikh, Alaullah; Charles, Richelle C; Sharmeen, Nusrat; Rollins, Sean M; Harris, Jason B; Bhuiyan, Md Saruar; Arifuzzaman, Mohammad; Khanam, Farhana; Bukka, Archana; Kalsy, Anuj; Porwollik, Steffen; Leung, Daniel T; Brooks, W Abdullah; LaRocque, Regina C; Hohmann, Elizabeth L; Cravioto, Alejandro; Logvinenko, Tanya; Calderwood, Stephen B; McClelland, Michael; Graham, James E; Qadri, Firdausi; Ryan, Edward T

2011-12-01

Salmonella enterica serotype Typhi is the cause of typhoid fever. It is a human-restricted pathogen, and few data exist on S. Typhi gene expression in humans. We applied an RNA capture and amplification technique, Selective Capture of Transcribed Sequences (SCOTS), and microarray hybridization to identify S. Typhi transcripts expressed in the blood of five humans infected with S. Typhi in Bangladesh. In total, we detected the expression of mRNAs for 2,046 S. Typhi genes (44% of the S. Typhi genome) in human blood; expression of 912 genes was detected in all 5 patients, and expression of 1,100 genes was detected in 4 or more patients. Identified transcripts were associated with the virulence-associated PhoP regulon, Salmonella pathogenicity islands, the use of alternative carbon and energy sources, synthesis and transport of iron, thiamine, and biotin, and resistance to antimicrobial peptides and oxidative stress. The most highly represented group were genes currently annotated as encoding proteins designated as hypothetical, unknown, or unclassified. Of the 2,046 detected transcripts, 1,320 (29% of the S. Typhi genome) had significantly different levels of detection in human blood compared to in vitro cultures; detection of 141 transcripts was significantly different in all 5 patients, and detection of 331 transcripts varied in at least 4 patients. These mRNAs encode proteins of unknown function, those involved in energy metabolism, transport and binding, cell envelope, cellular processes, and pathogenesis. We confirmed increased expression of a subset of identified mRNAs by quantitative-PCR. We report the first characterization of bacterial transcriptional profiles in the blood of patients with typhoid fever. S. Typhi is an important global pathogen whose restricted host range has greatly inhibited laboratory studies. Our results suggest that S. Typhi uses a largely uncharacterized genetic repertoire to survive within cells and utilize alternate energy sources during infection.

Typhoid fever in the United States, 1999-2006.

PubMed

Lynch, Michael F; Blanton, Elizabeth M; Bulens, Sandra; Polyak, Christina; Vojdani, Jazmin; Stevenson, Jennifer; Medalla, Felicia; Barzilay, Ezra; Joyce, Kevin; Barrett, Timothy; Mintz, Eric Daniel

2009-08-26

Typhoid fever in the United States has increasingly been due to infection with antimicrobial-resistant Salmonella ser Typhi. National surveillance for typhoid fever can inform prevention and treatment recommendations. To assess trends in infections with antimicrobial-resistant S. Typhi. Cross-sectional, laboratory-based surveillance study. We reviewed data from 1999-2006 for 1902 persons with typhoid fever who had epidemiologic information submitted to the Centers for Disease Control and Prevention (CDC) and 2016 S. Typhi isolates sent by participating public health laboratories to the National Antimicrobial Resistance Monitoring System Laboratory at the CDC for antimicrobial susceptibility testing. Proportion of S. Typhi isolates demonstrating resistance to 14 antimicrobial agents and patient risk factors for antimicrobial-resistant infections. Patient median age was 22 years (range, <1-90 years); 1295 (73%) were hospitalized and 3 (0.2%) died. Foreign travel within 30 days of illness was reported by 1439 (79%). Only 58 travelers (5%) had received typhoid vaccine. Two hundred seventy-two (13%) of 2016 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant S. Typhi [MDRST]); 758 (38%) were resistant to nalidixic acid (nalidixic acid-resistant S. Typhi [NARST]) and 734 NARST isolates (97%) had decreased susceptibility to ciprofloxacin. The proportion of NARST increased from 19% in 1999 to 54% in 2006. Five ciprofloxacin-resistant isolates were identified. Patients with resistant infections were more likely to report travel to the Indian subcontinent: 85% of patients infected with MDRST and 94% with NARST traveled to the Indian subcontinent, while 44% of those with susceptible infections did (MDRST odds ratio, 7.5; 95% confidence interval, 4.1-13.8; NARST odds ratio, 20.4; 95% confidence interval, 12.4-33.9). Infection with antimicrobial-resistant S. Typhi strains among US patients with typhoid fever is associated with travel to the Indian subcontinent, and an increasing proportion of these infections are due to S. Typhi strains with decreased susceptibility to fluoroquinolones.

A cross-sectional seroepidemiological survey of typhoid fever in Fiji

PubMed Central

Baker, Stephen; Lau, Colleen L.; Rawalai, Kitione; Taufa, Mere; Coriakula, Jerimaia; Thieu, Nga Tran Vu; Van, Tan Trinh; Ngoc, Dung Tran Thi; Hens, Niel; Lowry, John H.; de Alwis, Ruklanthi; Cano, Jorge; Jenkins, Kylie; Mulholland, E. Kim; Nilles, Eric J.; Kama, Mike; Edmunds, W. John

2017-01-01

Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks. PMID:28727726

A cross-sectional seroepidemiological survey of typhoid fever in Fiji.

PubMed

Watson, Conall H; Baker, Stephen; Lau, Colleen L; Rawalai, Kitione; Taufa, Mere; Coriakula, Jerimaia; Thieu, Nga Tran Vu; Van, Tan Trinh; Ngoc, Dung Tran Thi; Hens, Niel; Lowry, John H; de Alwis, Ruklanthi; Cano, Jorge; Jenkins, Kylie; Mulholland, E Kim; Nilles, Eric J; Kama, Mike; Edmunds, W John

2017-07-01

Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks.

[Enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Salmonella Typhi lipopolysaccharide O and capsular polysaccharide Vi antigens in persons from outbreak of typhoid fever].

PubMed

Rastawicki, Waldemar; Kałużewski, Stanisław

2015-01-01

The laboratory diagnosis of typhoid fever is dependent upon either isolation of S. Typhi from a clinical sample or the detection of raised titers of serum antibodies in the Widal test or the passive hemagglutination assay (PHA). In this study we evaluated the usefulness of ELISA for detection of antibodies to S. Typhi lipopolysaccharide O and capsular polysaccharide Vi antigens in the sera of persons from outbreak of typhoid fever. Fifteen serum samples from patients with laboratory confirmed typhoid fever and 140 sera from persons suspected for contact with typhoid fever patients from outbreak in 1974/75 in Poland were tested by ELISA. Additionally, as the control group, we tested 115 sera from blood donors for the presence of S. Typhi anti-LPS and anti-Vi antibodies. Anti-LPS and anti-Vi antibodies were detected in 80% and 53.3% of sera obtained from patients with laboratory confirmed typhoid fever, respectively. The high percentages of positive results in ELISA were also noted in the group of persons suspected for contact with typhoid fever patients (51.4% and 45%) but not in the group of blood donors (7.8% and 6.1%, respectively). The ELISA could be a useful tool for the serological diagnosis of typhoid fever in patients who have clinical symptoms but are culture negative, especially during massive outbreaks of typhoid fever.

DNA biosensor for detection of Salmonella typhi from blood sample of typhoid fever patient using gold electrode modified by self-assembled monolayers of thiols

NASA Astrophysics Data System (ADS)

Suryapratiwi, Windha Novita; Paat, Vlagia Indira; Gaffar, Shabarni; Hartati, Yeni Wahyuni

2017-05-01

Electrochemical biosensors are currently being developed in order to handle various clinical problems in diagnosing infectious diseases caused by pathogenic bacteria, or viruses. On this research, voltammetric DNA biosensor using gold electrode modified by thiols with self-assembled monolayers had been developed to detect a certain sequence of Salmonella typhi DNA from blood sample of typhoid fever patient. Thiol groups of cysteamines (Cys) and aldehyde groups from glutaraldehydes (Glu) were used as a link to increase the performance of gold electrode in detecting guanine oxidation signal of hybridized S. typhi DNA and ssDNA probe. Standard calibration method was used to determine analytical parameters from the measurements. The result shown that, the detection of S. typhi DNA from blood sample of typhoid fever patient can be carried out by voltammetry using gold electrode modified by self-assembled monolayers of thiols. A characteristic oxidation potential of guanine using Au/Cys/Gluwas obtained at +0.17 until +0.20 V. Limit of detection and limit of quantification from this measurements were 1.91μg mL-1 and 6.35 μg mL-1. The concentration of complement DNA from sample was 6.96 μg mL-1.

A brief review on the immunological scenario and recent developmental status of vaccines against enteric fever.

PubMed

Howlader, Debaki Ranjan; Koley, Hemanta; Maiti, Suhrid; Bhaumik, Ushasi; Mukherjee, Priyadarshini; Dutta, Shanta

2017-11-07

Enteric fever has been one of the leading causes of severe illness and deaths worldwide. S. Typhi and S. Paratyphi A, B and C are important enteric fever-causing organisms globally. This infection causes about 21 million cases among which 222,000 typhoid related deaths occurred in 2015. These estimates do not reflect the ultimate and real status of the disease due to the lack of unified diagnostic and proper reporting system from typhoid endemic and other regions. Current control strategies have become increasingly ineffective due to the emergence of multi-drug resistance among the strains. This situation worsens the disease-burden in developing as well as in developed countries. Moreover the emergence of S. Paratyphi A as a major enteric fever-causing organism in several Asian countries, demands a prophylactic measure at this hour. Other than two licensed vaccines of S. Typhi, there are no exsisting vaccines for S. Paratyphi A. Moreover, travelers returning from endemic regions are becoming more susceptible to have these infections. In this situation, a need for bivalent approach is required where a single immunogen (consisting from each organism) will be effective against the disease. In this review, we have focused on the general information about typhoidal fever, its spread and epidemiology in brief and the present status of typhoidal vaccines and its future. This review highlights existing gaps in the typhoidal salmonellae research with a special emphasis on the status of present typhoidal salmonellae vaccine research. Copyright © 2017 Elsevier Ltd. All rights reserved.

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever.

PubMed

Tran Vu Thieu, Nga; Trinh Van, Tan; Tran Tuan, Anh; Klemm, Elizabeth J; Nguyen Ngoc Minh, Chau; Voong Vinh, Phat; Pham Thanh, Duy; Ho Ngoc Dan, Thanh; Pham Duc, Trung; Langat, Pinky; Martin, Laura B; Galan, Jorge; Liang, Li; Felgner, Philip L; Davies, D Huw; de Jong, Hanna K; Maude, Rapeephan R; Fukushima, Masako; Wijedoru, Lalith; Ghose, Aniruddha; Samad, Rasheda; Dondorp, Arjen M; Faiz, Abul; Darton, Thomas C; Pollard, Andrew J; Thwaites, Guy E; Dougan, Gordon; Parry, Christopher M; Baker, Stephen

2017-08-01

The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease. IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid. We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

An Outpatient, Ambulant-Design, Controlled Human Infection Model Using Escalating Doses of Salmonella Typhi Challenge Delivered in Sodium Bicarbonate Solution

PubMed Central

Waddington, Claire S.; Darton, Thomas C.; Jones, Claire; Haworth, Kathryn; Peters, Anna; John, Tessa; Thompson, Ben A. V.; Kerridge, Simon A.; Kingsley, Robert A.; Zhou, Liqing; Holt, Kathryn E.; Yu, Ly-Mee; Lockhart, Stephen; Farrar, Jeremy J.; Sztein, Marcelo B.; Dougan, Gordon; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.

2014-01-01

Background. Typhoid fever is a major global health problem, the control of which is hindered by lack of a suitable animal model in which to study Salmonella Typhi infection. Until 1974, a human challenge model advanced understanding of typhoid and was used in vaccine development. We set out to establish a new human challenge model and ascertain the S. Typhi (Quailes strain) inoculum required for an attack rate of 60%–75% in typhoid-naive volunteers when ingested with sodium bicarbonate solution. Methods. Groups of healthy consenting adults ingested escalating dose levels of S. Typhi and were closely monitored in an outpatient setting for 2 weeks. Antibiotic treatment was initiated if typhoid diagnosis occurred (temperature ≥38°C sustained ≥12 hours or bacteremia) or at day 14 in those remaining untreated. Results. Two dose levels (103 or 104 colony-forming units) were required to achieve the primary objective, resulting in attack rates of 55% (11/20) or 65% (13/20), respectively. Challenge was well tolerated; 4 of 40 participants fulfilled prespecified criteria for severe infection. Most diagnoses (87.5%) were confirmed by blood culture, and asymptomatic bacteremia and stool shedding of S. Typhi was also observed. Participants who developed typhoid infection demonstrated serological responses to flagellin and lipopolysaccharide antigens by day 14; however, no anti-Vi antibody responses were detected. Conclusions. Human challenge with a small inoculum of virulent S. Typhi administered in bicarbonate solution can be performed safely using an ambulant-model design to advance understanding of host–pathogen interactions and immunity. This model should expedite development of diagnostics, vaccines, and therapeutics for typhoid control. PMID:24519873

[Report of Relapse Typhoid Fever Cases from Kolkata, India: Recrudescence or Reinfection?

PubMed

Samajpati, Sriparna; Das, Surojit; Ray, Ujjwayini; Dutta, Shanta

2018-05-24

Three relapse cases were reported out of 107 hospital-attending typhoid cases within a period of 2 years (2014-2016) from Apollo Gleneagles Hospital, Kolkata, India. During the first episode of typhoid fever, 2 of the 3 cases were treated with ceftriaxone (CRO) for 7 days, and 1 was treated for 14 days. Six Salmonella Typhi (S. Typhi) isolates, obtained from the 3 patients during both typhoid episodes, were subjected to antimicrobial susceptibility testing, detection of quinolone resistance-determining region (QRDR) mutation and molecular subtyping by pulsed-field gel electrophoresis (PFGE), multiple-locus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), clustered regularly interspaced short palindromic repeats (CRISPR), and H58 haplotyping. Pairs of the S. Typhi strains isolated from two of the patients during the 1st and 2nd episodes were similar with respect to the antimicrobial resistance (AMR) profiles, QRDR mutations, and molecular subtypes; whereas, the S. Typhi strain pair isolated from the 3rd patient were different in their AMR profiles, QRDR mutations, and MLVA profiles. From these observations, it may be concluded that in spite of treating typhoid cases with CRO for 7-14 days, relapse of typhoid fever might occur. The article also showed the advantage of MLVA typing over PFGE, MLST, and CRISPR typing for the discrimination of strains isolated from the same patient in case of relapse of typhoid fever.

[Formation and persistence of L-variants of Salmonella typhi in experimental typhoid and in carriers].

PubMed

Levina, G A; Prozorovskiĭ, S V; Iagud, S L; Grumman, M I; Gorelov, A L

1981-07-01

The possibility of the induction and persistence of S. typhi L-forms in the process of experimental typhoid infection and carriership has been studied in rabbits. This study has revealed that the process of L-transformation leading to the appearance of the imbalanced growth forms and unstable L-forms of S. typhi in the organism of the animals infected with S. typhi culture may occur under the conditions of carriership. Such changed forms can be detected in the organism of the animals 18 months after the primary infection.

The diagnostic accuracy of three rapid diagnostic tests for typhoid fever at Chittagong Medical College Hospital, Chittagong, Bangladesh.

PubMed

Maude, Rapeephan R; de Jong, Hanna K; Wijedoru, Lalith; Fukushima, Masako; Ghose, Aniruddha; Samad, Rasheda; Hossain, Mohammed Amir; Karim, Mohammed Rezaul; Faiz, Mohammed Abul; Parry, Christopher M

2015-10-01

To determine the diagnostic accuracy of three rapid diagnostic tests (RDTs) for typhoid fever in febrile hospitalised patients in Bangladesh. Febrile adults and children admitted to Chittagong Medical College Hospital, Bangladesh, were investigated with Bact/Alert(®) blood cultures and real-time PCR to detect Salmonella enterica Typhi and Paratyphi A and assays for Rickettsia, leptospirosis and dengue fever. Acute serum samples were examined with the LifeAssay (LA) Test-it™ Typhoid IgM lateral flow assay detecting IgM antibodies against S. Typhi O antigen, CTKBiotech Onsite Typhoid IgG/IgM Combo Rapid-test cassette lateral flow assay detecting IgG and IgM antibodies against S. Typhi O and H antigens and SD Bioline line assay for IgG and IgM antibodies against S. Typhi proteins. In 300 malaria smear-negative febrile patients [median (IQR) age of 13.5 (5-31) years], 34 (11.3%) had confirmed typhoid fever: 19 positive by blood culture for S. Typhi (three blood PCR positive) and 15 blood culture negative but PCR positive for S. Typhi in blood. The respective sensitivity and specificity of the three RDTs in patients using a composite reference standard of blood culture and/or PCR-confirmed typhoid fever were 59% and 61% for LifeAssay, 59% and 74% for the CTK IgM and/or IgG, and 24% and 96% for the SD Bioline RDT IgM and/or IgG. The LifeAssay RDT had a sensitivity of 63% and a specificity of 91% when modified with a positive cut-off of ≥2+ and analysed using a Bayesian latent class model. These typhoid RDTs demonstrated moderate diagnostic accuracies, and better tests are needed. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Serology of Typhoid Fever in an Area of Endemicity and Its Relevance to Diagnosis

PubMed Central

House, Deborah; Wain, John; Ho, Vo A.; Diep, To S.; Chinh, Nguyen T.; Bay, Phan V.; Vinh, Ha; Duc, Minh; Parry, Christopher M.; Dougan, Gordon; White, Nicholas J.; Hien, Tran Tinh; Farrar, Jeremy J.

2001-01-01

Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam in which typhoid is endemic, and their usefulness for the diagnosis of typhoid fever was evaluated. The antibody responses to both antigens were highly variable among individuals infected with serotype Typhi, and elevated antibody titers were also detected in a high proportion of serum samples from healthy subjects from the community. In-house enzyme-linked immunosorbent assays (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum antibodies were compared with other serologically based tests for the diagnosis of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM] dipstick, and IDeaL TUBEX). At a specificity of ≥0.93, the sensitivities of the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity, 0.87; specificity, 0.76). The serological assays based on the detection of IgM antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick) had a significantly higher sensitivity than the Widal TO test when used with a single acute-phase serum sample (P ≤ 0.007). These tests could be of use for the diagnosis of typhoid fever in patients who have clinical typhoid fever but are culture negative or in regions where bacterial culturing facilities are not available. PMID:11230418

Ancient typhoid epidemic reveals possible ancestral strain of Salmonella enterica serovar Typhi.

PubMed

Papagrigorakis, Manolis J; Synodinos, Philippos N; Yapijakis, Christos

2007-01-01

In contrast to other serotypes of Salmonella enterica, S. Typhi is exclusively adapted to human hosts. Recently, S. Typhi was identified in ancient skeletal material, thereby incriminating typhoid fever for the Plague of Athens. Since, according to Thucydides' report, animals were also affected by the disease, a working hypothesis is constituted that the causative agent of the Plague might be the anticipated original strain of S. Typhi, purportedly capable of infecting animals as well as humans. Possible future sequencing of the discovered ancient strain of S. Typhi may help towards identifying its genomic differences responsible for its modern specification to humans.

Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E

PubMed Central

Karavolos, Michail H; Bulmer, David M; Spencer, Hannah; Rampioni, Giordano; Schmalen, Ira; Baker, Stephen; Pickard, Derek; Gray, Joe; Fookes, Maria; Winzer, Klaus; Ivens, Alasdair; Dougan, Gordon; Williams, Paul; Khan, C M Anjam

2011-01-01

Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling. PMID:21331094

Proteomics Analysis of the Causative Agent of Typhoid Fever

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ansong, Charles; Yoon, Hyunjin; Norbeck, Angela D.

2008-02-01

Typhoid fever is a potentially fatal disease caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. typhi). S. typhi infection is a complex process that involves numerous bacterially-encoded virulence determinants, and these are thought to confer both stringent human host specificity and a high mortality rate. In the present study we used a liquid chromatography-mass spectrometry (LC-MS) based proteomics strategy to investigate the proteome of logarithmic, stationary phase, and low pH/low magnesium (MgM) S. typhi cultures. This represents the first large scale comprehensive characterization of the S. typhi proteome. Our analysis identified a total of 2066 S. typhi proteins.more » In an effort to identify putative S. typhi-specific virulence factors, we then compared our S. typhi results to those obtained in a previously published study of the S. typhimurium proteome under similar conditions (Adkins J.N. et al (2006) Mol Cell Prot). Comparative proteomic analysis of S. typhi (strain Ty2) and S. typhimurium (strains LT2 and 14028) revealed a subset of highly expressed proteins unique to S. typhi that were exclusively detected under conditions that mimic the infective state in macrophage cells. These proteins included CdtB, HlyE, and a conserved protein encoded by t1476. The differential expression of selected proteins was confirmed by Western blot analysis. Taken together with the current literature, our observations suggest that this subset of proteins may play a role in S. typhi pathogenesis and human host specificity. In addition, we observed products of the biotin (bio) operon displayed a higher abundance in the more virulent strains S. typhi-Ty2 and S. typhimurium-14028 compared to the virulence attenuated S. typhimurium strain LT2, suggesting bio proteins may contribute to Salmonella pathogenesis.« less

Association of carcinoma of the gallbladder with typhoid carriage in a typhoid endemic area using nested PCR.

PubMed

Nath, Gopal; Singh, Yogesh Kumar; Kumar, Kailash; Gulati, Anil Kumar; Shukla, Vijay Kumar; Khanna, Ajay Kumar; Tripathi, Sunil Kumar; Jain, Ashok Kumar; Kumar, Mohan; Singh, Tej Bali

2008-08-30

Although well studied the association between chronic typhoid carrier state and carcinoma of the gallbladder (CaGB) remains unproven. The study was performed at a tertiary care medical center in North India and involved 52 patients with CaGB, 223 patients with benign gallbladder diseases, 508 healthy individuals and, 424 corpses. For the detection of Salmonella enterica serovar Typhi, hepatobiliary specimens were subjected to DNA extraction for specific nested- PCR amplification of the S. Typhi flagellin gene. Anti-Vi S. Typhi antibodies were detected in serum samples from patients by indirect haemagglutination. Thirty five of the 52 (67.3%) CaGB patients were PCR-positive for the S. Typhi flagellin gene; significantly higher than for patients with benign gallbladder diseases (95/223, 42.6%; p<0.01) and corpses (35/424, 8.2%; p<0.001). The numbers of individuals that had significant anti-Vi antibody titres (> or = 160) in their serum were 20/52 (38.5%) for CaGB patients, 31/223 (13.9%) for patients with benign gallbladder diseases, and 47/508 (9.2%) for healthy individuals. Specific nested-PCR amplification of the S. Typhi flagellin gene in hepato-biliary specimens was more sensitive for detection of S. Typhi carriage than anti-Vi antibody titres in serum. The results demonstrate an association between typhoid carriage and gallbladder diseases, both CaGB and benign. S. Typhi specific immunosuppression is also suggested in patients with gallbladder diseases.

Typhoid Fever in South Africa in an Endemic HIV Setting

PubMed Central

Keddy, Karen H.; Sooka, Arvinda; Smith, Anthony M.; Musekiwa, Alfred; Tau, Nomsa P.; Klugman, Keith P.; Angulo, Frederick J.

2016-01-01

Background Typhoid fever remains an important disease in Africa, associated with outbreaks and the emerging multidrug resistant Salmonella enterica serotype Typhi (Salmonella Typhi) haplotype, H58. This study describes the incidence of, and factors associated with mortality due to, typhoid fever in South Africa, where HIV prevalence is high. Methods and Findings Nationwide active laboratory-based surveillance for culture-confirmed typhoid fever was undertaken from 2003–2013. At selected institutions, additional clinical data from patients were collected including age, sex, HIV status, disease severity and outcome. HIV prevalence among typhoid fever patients was compared to national HIV seroprevalence estimates. The national reference laboratory tested Salmonella Typhi isolates for antimicrobial susceptibility and haplotype. Unadjusted and adjusted logistic regression analyses were conducted determining factors associated with typhoid fever mortality. We identified 855 typhoid fever cases: annual incidence ranged from 0.11 to 0.39 per 100,000 population. Additional clinical data were available for 369 (46.8%) cases presenting to the selected sites. Among typhoid fever patients with known HIV status, 19.3% (29/150) were HIV-infected. In adult females, HIV prevalence in typhoid fever patients was 43.2% (19/44) versus 15.7% national HIV seroprevalence (P < .001); in adult males, 16.3% (7/43) versus 12.3% national HIV seroprevalence (P = .2). H58 represented 11.9% (22/185) of Salmonella Typhi isolates tested. Increased mortality was associated with HIV infection (AOR 10.7; 95% CI 2.3–50.3) and disease severity (AOR 9.8; 95% CI 1.6–60.0) on multivariate analysis. Conclusions Typhoid fever incidence in South Africa was largely unchanged from 2003–2013. Typhoid fever mortality was associated disease severity. HIV infection may be a contributing factor. Interventions mandate improved health care access, including to HIV management programmes as well as patient education. Further studies are necessary to clarify relationships between HIV infection and typhoid fever in adults. PMID:27780232

Typhoid Fever in South Africa in an Endemic HIV Setting.

PubMed

Keddy, Karen H; Sooka, Arvinda; Smith, Anthony M; Musekiwa, Alfred; Tau, Nomsa P; Klugman, Keith P; Angulo, Frederick J

2016-01-01

Typhoid fever remains an important disease in Africa, associated with outbreaks and the emerging multidrug resistant Salmonella enterica serotype Typhi (Salmonella Typhi) haplotype, H58. This study describes the incidence of, and factors associated with mortality due to, typhoid fever in South Africa, where HIV prevalence is high. Nationwide active laboratory-based surveillance for culture-confirmed typhoid fever was undertaken from 2003-2013. At selected institutions, additional clinical data from patients were collected including age, sex, HIV status, disease severity and outcome. HIV prevalence among typhoid fever patients was compared to national HIV seroprevalence estimates. The national reference laboratory tested Salmonella Typhi isolates for antimicrobial susceptibility and haplotype. Unadjusted and adjusted logistic regression analyses were conducted determining factors associated with typhoid fever mortality. We identified 855 typhoid fever cases: annual incidence ranged from 0.11 to 0.39 per 100,000 population. Additional clinical data were available for 369 (46.8%) cases presenting to the selected sites. Among typhoid fever patients with known HIV status, 19.3% (29/150) were HIV-infected. In adult females, HIV prevalence in typhoid fever patients was 43.2% (19/44) versus 15.7% national HIV seroprevalence (P < .001); in adult males, 16.3% (7/43) versus 12.3% national HIV seroprevalence (P = .2). H58 represented 11.9% (22/185) of Salmonella Typhi isolates tested. Increased mortality was associated with HIV infection (AOR 10.7; 95% CI 2.3-50.3) and disease severity (AOR 9.8; 95% CI 1.6-60.0) on multivariate analysis. Typhoid fever incidence in South Africa was largely unchanged from 2003-2013. Typhoid fever mortality was associated disease severity. HIV infection may be a contributing factor. Interventions mandate improved health care access, including to HIV management programmes as well as patient education. Further studies are necessary to clarify relationships between HIV infection and typhoid fever in adults.

Immunoproteomic analysis of antibody in lymphocyte supernatant in patients with typhoid fever in Bangladesh.

PubMed

Charles, Richelle C; Liang, Li; Khanam, Farhana; Sayeed, M Abu; Hung, Chris; Leung, Daniel T; Baker, Stephen; Ludwig, Albrecht; Harris, Jason B; Larocque, Regina C; Calderwood, Stephen B; Qadri, Firdausi; Felgner, Philip L; Ryan, Edward T

2014-03-01

We have previously shown that an assay based on detection of anti-Salmonella enterica serotype Typhi antibodies in supernatant of lymphocytes harvested from patients presenting with typhoid fever (antibody in lymphocyte supernatant [ALS] assay) can identify 100% of patients with blood culture-confirmed typhoid fever in Bangladesh. In order to define immunodominant proteins within the S. Typhi membrane preparation used as antigen in these prior studies and to identify potential biomarkers unique to S. Typhi bacteremic patients, we probed microarrays containing 2,724 S. Typhi proteins with ALS collected at the time of clinical presentation from 10 Bangladeshis with acute typhoid fever. We identified 62 immunoreactive antigens when evaluating both the IgG and IgA responses. Immune responses to 10 of these antigens discriminated between individuals with acute typhoid infection and healthy control individuals from areas where typhoid infection is endemic, as well as Bangladeshi patients presenting with fever who were subsequently confirmed to have a nontyphoid illness. Using an ALS enzyme-linked immunosorbent assay (ELISA) format and purified antigen, we then confirmed that immune responses against the antigen with the highest immunoreactivity (hemolysin E [HlyE]) correctly identified individuals with acute typhoid or paratyphoid fever in Dhaka, Bangladesh. These observations suggest that purified antigens could be used with ALS and corresponding acute-phase activated B lymphocytes in diagnostic platforms to identify acutely infected patients, even in areas where enteric fever is endemic.

Expression and function of S100A8/A9 (calprotectin) in human typhoid fever and the murine Salmonella model.

PubMed

De Jong, Hanna K; Achouiti, Ahmed; Koh, Gavin C K W; Parry, Christopher M; Baker, Stephen; Faiz, Mohammed Abul; van Dissel, Jaap T; Vollaard, Albert M; van Leeuwen, Ester M M; Roelofs, Joris J T H; de Vos, Alex F; Roth, Johannes; van der Poll, Tom; Vogl, Thomas; Wiersinga, Willem Joost

2015-04-01

Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice.

Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model

PubMed Central

De Jong, Hanna K.; Achouiti, Ahmed; Koh, Gavin C. K. W.; Parry, Christopher M.; Baker, Stephen; Faiz, Mohammed Abul; van Dissel, Jaap T.; Vollaard, Albert M.; van Leeuwen, Ester M. M.; Roelofs, Joris J. T. H.; de Vos, Alex F.; Roth, Johannes; van der Poll, Tom; Vogl, Thomas; Wiersinga, Willem Joost

2015-01-01

Background Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. Methods and principal findings S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. Conclusion S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice. PMID:25860480

Changing Patterns in Enteric Fever Incidence and Increasing Antibiotic Resistance of Enteric Fever Isolates in the United States, 2008–2012

PubMed Central

Date, Kashmira A.; Newton, Anna E.; Medalla, Felicita; Blackstock, Anna; Richardson, LaTonia; McCullough, Andre; Mintz, Eric D.; Mahon, Barbara E.

2016-01-01

Background Enteric fever in the United States has been primarily associated with travel and with worrisome changes in global patterns of antimicrobial resistance. We present the first comprehensive report of National Typhoid and Paratyphoid Fever Surveillance System (NTPFS) data for a 5-year period (2008–2012). Methods We reviewed data on laboratory-confirmed cases reported to NTPFS, and related antimicrobial susceptibility results of Salmonella Typhi and Paratyphi A isolates sent for testing by participating public health laboratories to the Centers for Disease Control and Prevention’s National Antimicrobial Resistance Monitoring System laboratory. Results During 2008–2012, 2341 enteric fever cases were reported, 80% typhoid and 20% paratyphoid A. The proportion caused by paratyphoid A increased from 16% (2008) to 22% (2012). Foreign travel within 30 days preceding illness onset was reported by 1961 (86%) patients (86% typhoid and 92% paratyphoid A). Travel to southern Asia was common (82% for typhoid, 97% for paratyphoid A). Among 1091 (58%) typhoid and 262 (56%) paratyphoid A isolates tested for antimicrobial susceptibility, the proportion resistant to nalidixic acid (NAL-R) increased from 2008 to 2012 (Typhi, 60% to 68%; Paratyphi A, 91% to 94%). Almost all NAL-R isolates were resistant or showed decreased susceptibility to ciprofloxacin. Resistance to at least ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug resistant [MDR]) was limited to Typhi isolates, primarily acquired in southern Asia (13%). Most MDR isolates were also NAL-R. Conclusions Enteric fever in the United States is primarily associated with travel to southern Asia, and increasing resistance is adding to treatment challenges. A bivalent typhoid and paratyphoid vaccine is needed. PMID:27090993

Changing Patterns in Enteric Fever Incidence and Increasing Antibiotic Resistance of Enteric Fever Isolates in the United States, 2008-2012.

PubMed

Date, Kashmira A; Newton, Anna E; Medalla, Felicita; Blackstock, Anna; Richardson, LaTonia; McCullough, Andre; Mintz, Eric D; Mahon, Barbara E

2016-08-01

Enteric fever in the United States has been primarily associated with travel and with worrisome changes in global patterns of antimicrobial resistance. We present the first comprehensive report of National Typhoid and Paratyphoid Fever Surveillance System (NTPFS) data for a 5-year period (2008-2012). We reviewed data on laboratory-confirmed cases reported to NTPFS, and related antimicrobial susceptibility results of Salmonella Typhi and Paratyphi A isolates sent for testing by participating public health laboratories to the Centers for Disease Control and Prevention's National Antimicrobial Resistance Monitoring System laboratory. During 2008-2012, 2341 enteric fever cases were reported, 80% typhoid and 20% paratyphoid A. The proportion caused by paratyphoid A increased from 16% (2008) to 22% (2012). Foreign travel within 30 days preceding illness onset was reported by 1961 (86%) patients (86% typhoid and 92% paratyphoid A). Travel to southern Asia was common (82% for typhoid, 97% for paratyphoid A). Among 1091 (58%) typhoid and 262 (56%) paratyphoid A isolates tested for antimicrobial susceptibility, the proportion resistant to nalidixic acid (NAL-R) increased from 2008 to 2012 (Typhi, 60% to 68%; Paratyphi A, 91% to 94%). Almost all NAL-R isolates were resistant or showed decreased susceptibility to ciprofloxacin. Resistance to at least ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug resistant [MDR]) was limited to Typhi isolates, primarily acquired in southern Asia (13%). Most MDR isolates were also NAL-R. Enteric fever in the United States is primarily associated with travel to southern Asia, and increasing resistance is adding to treatment challenges. A bivalent typhoid and paratyphoid vaccine is needed. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chemical closet treatment of typhoid carrier faeces.

PubMed

Harvey, R W; Price, T H

1972-09-01

An investigation to test the efficiency of chemical closets in treating excreta from typhoid carriers is described. The use of these closets kept a stream, which had in the past frequently contained Salmonella typhi, typhoid free for 24 months. Selenite broth as made in this laboratory, containing a final concentration of 0.8% sodium hydrogen selenite when inoculated with the water sample, was significantly better than commercial selenite brilliant green enrichment broth for the recovery of S. typhi.

Encephalitis in a traveller with typhoid fever: efficacy of corticosteroids.

PubMed

Mellon, Guillaume; Eme, Anne-Line; Rohaut, Benjamin; Brossier, Florence; Epelboin, Loïc; Caumes, Eric

2017-09-01

Typhoid fever is a bacterial infection caused by Salmonella typhi or S. paratyphi, recognized as a classical cause of fever in returning travellers. However, neuropsychiatric presentations are rarely reported in travellers diagnosed in western countries, whereas they are more commonly described in patients treated in endemic areas. We describe such a case and discuss the pathophysiologic mechanisms of this complication. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Epidemiology and risk factors for endemic typhoid fever in Uzbekistan.

PubMed

Srikantiah, Padmini; Vafokulov, Sagdullo; Luby, Stephen P; Ishmail, Tharwat; Earhart, Kenneth; Khodjaev, Ne'mat; Jennings, Gregory; Crump, John A; Mahoney, Frank J

2007-07-01

To investigate the risk factors for infection with endemic typhoid fever in the Samarkand region of Uzbekistan. Case-control study of culture-confirmed bloodstream infection with Salmonella Typhi. Patients were compared to age-matched community controls. Salmonella Typhi isolates were tested for antimicrobial susceptibility. We enrolled 97 patients and 192 controls. The median age of patients was 19 years. In a conditional regression model, consumption of unboiled surface water outside the home [adjusted odds ratio (aOR)=3.0, 95% confidence interval (CI)=1.1-8.2], use of antimicrobials in the 2 weeks preceding onset of symptoms (aOR=12.2, 95% CI 4.0-37.0), and being a student (aOR=4.0, 95% CI 1.4-11.3) were independently associated with typhoid fever. Routinely washing vegetables (aOR 0.06, 95% CI 0.02-0.2) and dining at a tea-house (aOR 0.4, 95% CI 0.2-1.0) were associated with protection against illness. Salmonella Typhi resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole was identified in 6 (15%) of 41 isolates tested. Endemic typhoid fever in Uzbekistan is transmitted by contaminated water. Recent use of antimicrobials also increased risk of infection. Targeted efforts at improving drinking water quality, especially for students and young adults, are likely to decrease transmission of typhoid fever. Measures to decrease the unnecessary use of antimicrobials would be expected to reduce the risk of typhoid fever and decrease the spread of multiple drug-resistant Salmonella Typhi.

Expression of intra- and extracellular granzymes in patients with typhoid fever.

PubMed

de Jong, Hanna K; Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J; Parry, Christopher M; Maude, Rapeephan R; Dondorp, Arjen M; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-07-01

Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.

Expression of intra- and extracellular granzymes in patients with typhoid fever

PubMed Central

Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J.; Parry, Christopher M.; Maude, Rapeephan R.; Dondorp, Arjen M.; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-01-01

Background Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. Methods and principal findings We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. Conclusion The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease. PMID:28749963

Development of a Live Attenuated Bivalent Oral Vaccine Against Shigella sonnei Shigellosis and Typhoid Fever.

PubMed

Wu, Yun; Chakravarty, Sumana; Li, Minglin; Wai, Tint T; Hoffman, Stephen L; Sim, B Kim Lee

2017-01-15

Shigella sonnei and Salmonella Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated S. Typhi vaccine (Ty21a) by using it as a vector to develop a bivalent oral vaccine to protect against S. sonnei shigellosis and typhoid fever. We recombineered the S. sonnei form I O-antigen gene cluster into the Ty21a chromosome to create Ty21a-Ss, which stably expresses S. sonnei form I O antigen. To enhance survivability in the acid environment of the stomach, we created an acid-resistant strain, Ty21a-AR-Ss, by inserting Shigella glutaminase-glutamate decarboxylase systems coexpressed with S. sonnei form I O-antigen gene. Mice immunized intranasally with Ty21a-AR-Ss produced antibodies against S. sonnei and S. Typhi, and survived lethal intranasal S. sonnei challenge. This paves the way for proposed good manufacturing practices manufacture and clinical trials intended to test the clinical effectiveness of Ty21a-AR-Ss in protecting against S. sonnei shigellosis and typhoid fever, as compared with the current Ty21a vaccine. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Lest We Forget: A Critical Analysis of Bioterrorist Incidents, National Exercises, and U.S. Prevention, Response and Recovery Strategies

DTIC Science & Technology

2011-04-01

American Type Culture Collection (ATCC), including Salmonella typhi (causes typhoid fever), Fancisella tularensis (causes tularemia ), Salmonella...incident, the Rajneesh cult obtained the agents on which it experimented, and Iraq obtained some of its lethal strains of anthrax, tularemia and

Epidemiology, clinical manifestations, and molecular typing of salmonella typhi isolated from patients with typhoid fever in Lebanon.

PubMed

Kanj, Souha S; Kanafani, Zeina A; Shehab, Marwa; Sidani, Nisreen; Baban, Tania; Baltajian, Kedak; Dakdouki, Ghenwa K; Zaatari, Mohamad; Araj, George F; Wakim, Rima Hanna; Dbaibo, Ghassan; Matar, Ghassan M

2015-06-01

The objective of this study was to examine the epidemiology and the clinical manifestations of typhoid fever as well as the susceptibility and strain relatedness of Salmonella typhi isolates in Lebanon from 2006 to 2007. A total of 120 patients with typhoid fever were initially identified from various areas of the country based on positive culture results for S. typhi from blood, urine, stools, bone marrow and/or positive serology. Clinical, microbiological and molecular analysis was performed on cases with complete data available. These results indicated that drinking water was an unlikely mode of transmission of the infection. Despite increasing reports of antimicrobial resistance among S. typhi isolates, the vast majority of these isolates were susceptible to various antibiotic agents, including ampicillin, cephalosporins, quinolones, and trimethoprim/sulfamethoxazole. Molecular analysis of the isolates revealed a predominance of one single genotype with no variation in distribution across the geographical regions. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Role of Environmental Factors in Shaping Spatial Distribution of Salmonella enterica Serovar Typhi, Fiji.

PubMed

de Alwis, Ruklanthi; Watson, Conall; Nikolay, Birgit; Lowry, John H; Thieu, Nga Tran Vu; Van, Tan Trinh; Ngoc, Dung Tran Thi; Rawalai, Kitione; Taufa, Mere; Coriakula, Jerimaia; Lau, Colleen L; Nilles, Eric J; Edmunds, W John; Kama, Mike; Baker, Stephen; Cano, Jorge

2018-02-01

Fiji recently experienced a sharp increase in reported typhoid fever cases. To investigate geographic distribution and environmental risk factors associated with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional cluster survey with associated serologic testing for Vi capsular antigen-specific antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots with high seroprevalence of Vi-specific antibodies were identified in northeastern mainland Fiji. Risk for Vi seropositivity increased with increased annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and decreased with increased distance from major rivers and creeks (OR 0.89/km increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR 0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi and its spatial distribution in Fiji are driven by environmental factors. Our findings can directly affect typhoid fever control efforts in Fiji.

Typhoid fever.

PubMed

Wain, John; Hendriksen, Rene S; Mikoleit, Matthew L; Keddy, Karen H; Ochiai, R Leon

2015-03-21

Control of typhoid fever relies on clinical information, diagnosis, and an understanding for the epidemiology of the disease. Despite the breadth of work done so far, much is not known about the biology of this human-adapted bacterial pathogen and the complexity of the disease in endemic areas, especially those in Africa. The main barriers to control are vaccines that are not immunogenic in very young children and the development of multidrug resistance, which threatens efficacy of antimicrobial chemotherapy. Clinicians, microbiologists, and epidemiologists worldwide need to be familiar with shifting trends in enteric fever. This knowledge is crucial, both to control the disease and to manage cases. Additionally, salmonella serovars that cause human infection can change over time and location. In areas of Asia, multidrug-resistant Salmonella enterica serovar Typhi (S Typhi) has been the main cause of enteric fever, but now S Typhi is being displaced by infections with drug-resistant S enterica serovar Paratyphi A. New conjugate vaccines are imminent and new treatments have been promised, but the engagement of local medical and public health institutions in endemic areas is needed to allow surveillance and to implement control measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Latex agglutination test (LAT) for the diagnosis of typhoid fever.

PubMed

Sahni, Gopal Shankar

2013-06-01

The efficacy of latex agglutination test in the rapid diagnosis of typhoid fever was studied and the result compared with that of blood culture. This study included 80 children suffering from typhoid fever, among which 40 were confirmed by blood culture isolation and 40 had possible typhoid fever based on high Widal's titre (a four-fold rise in the titre of antibody to typhi "O" and "H" antigen was considered as a positive Widal's test result). Eighty children, 40 with febrile illness confirmed to be other than typhoid and 40 normal healthy children were used as negative controls. The various groups were: (i) Study group ie, group I had 40 children confirmed by culture isolation of Salmonella typhi(confirmed typhoid cases). (ii) Control groups ie, (a) group II with 40 febrile controls selected from paediatrics ward where cause other than S typhi has been established, (b) group III with 40 afebrile healthy controls that were siblings of the children admitted in paediatric ward for any reason with no history of fever and TAB vaccination in the last one year, and (c) group IV with 40 children with high Widal's titre in paired sera sample. Widal's test with paired sera with a one week interval between collections were done in all 40 patients. Latex aggtutination test which could detect 900 ng/ml of antigen as observed in checker board titration, was positive in all 40 children from group I who had positive blood culture and in 30 children from group IV who had culture negative and had high Widal's titre positive. Latex agglutination test was positive in 4 children in group II and none in group III. Using blood culture positive cases as true positive and children in groups II and III as true negative, the test had a sensitivity of 100% and specificity of 96%. Latex agglutination test was found to be significantly sensitive (100%) and specific (96%) and could detect 75% more cases in group IV (possible typhoid cases). Thus latex agglutination test can be used for rapid diagnosis of typhoid fever though it cannot replace conventional blood culture required for isolation of organism to report the antibiotic sensitivity.

Standardisation of polymerase chain reaction for the detection of Salmonella typhi in typhoid fever.

PubMed Central

Chaudhry, R; Laxmi, B V; Nisar, N; Ray, K; Kumar, D

1997-01-01

To improve the diagnosis of Salmonella typhi infection, a polymerase chain reaction (PCR) assay was developed for the amplification of the dH flagellin gene of S typhi. Primers were designed from dH flagellin gene sequence which will give an amplification product of 486 base pairs. In tests to study the specificity of the assay, no amplification was seen in non-salmonella strains or salmonella strains with flagellar gene other than "d". Sensitivity tests determined that 28 pg of S typhi target DNA or 3 x 10(2) target bacteria could be detected by the PCR assay. Subsequently, the PCR technique was used for detection of S typhi in blood or clot cultures from 84 patients clinically suspected of having typhoid fever, and from 20 healthy control subjects. Twenty five of 84 samples from clinically suspected cases were positive by PCR; four of which were culture negative. No amplification was seen in samples from patients who were culture positive for organisms other than S typhi or from controls. The time taken for each sample for PCR analysis was less than 48 hours compared with three to five days for blood or clot culture. PCR appeared to be a promising diagnostic test for typhoid fever. Images PMID:9215131

Changing trends of culture-positive typhoid fever and antimicrobial susceptibility in a tertiary care North Indian Hospital over the last decade.

PubMed

Sharma, Priyanka; Dahiya, Sushila; Manral, Neelam; Kumari, Bhavana; Kumar, Sambuddha; Pandey, Sangeeta; Sood, Seema; Das, Bimal Kumar; Kapil, Arti

2018-01-01

The present study was undertaken to analyse the trend in prevalence of culture-positive typhoid fever during the last decade and to determine antimicrobial susceptibility profile of Salmonella Typhi and Salmonella Paratyphi A isolated from patients of enteric fever presenting to our hospital. All the culture-positive enteric fever cases during 2005-2016 presenting to our Hospital were included in the study. Antimicrobial susceptibility was done against chloramphenicol, amoxicillin, co-trimoxazole, ciprofloxacin, ofloxacin, levofloxacin, pefloxacin, ceftriaxone and azithromycin as per corresponding CLSI guidelines for each year. We also analysed the proportion of culture positivity during 1993-2016 in light of the antibiotic consumption data from published literature. A total of 1066 strains-S. Typhi (772) and S. Paratyphi A (294) were isolated from the blood cultures during the study. A maximum number of cases were found in July-September. Antimicrobial susceptibility for chloramphenicol, amoxicillin and co-trimoxazole was found to be 87.9%, 75.5%, 87.3% for S. Typhi and 94.2%, 90.1% and 94.2% for S. Paratyphi A, respectively. Ciprofloxacin, ofloxacin and levofloxacin susceptibility were 71.3%, 70.8% and 70.9% for S. Typhi and 58.1%, 57.4% and 57.1% for S. Paratyphi A, respectively. Azithromycin susceptibility was 98.9% in S. Typhi. Although susceptibility to ceftriaxone and cefixime was 100% in our isolates, there is a continuous increase in ceftriaxone minimum inhibitory concentration (MIC) 50 and MIC 90 values over the time. The proportion of blood culture-positive cases during 1993-2016 ranged from a minimum of 0.0006 in 2014 to a maximum of 0.0087 in 1999. We found that the most common etiological agent of enteric fever is S. Typhi causing the majority of cases from July to October in our region. MIC to ceftriaxone in typhoidal salmonellae is creeping towards resistance and more data are needed to understand the azithromycin susceptibility.

Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

PubMed

Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

2015-06-01

A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h) and/or microbiological (S. Typhi bacteremia) endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-). Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD-) were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h). Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.

Rhabdomyolysis Complicating Typhoid Fever in A Child and Review of the Literature.

PubMed

Snelling, Peter James; Moriarty, Paul; Vaska, Vikram L; Levitt, David; Nourse, Clare

2017-09-01

Typhoid fever is an important cause of morbidity and mortality in the developing world, particularly in children, but is infrequently observed in the developed world and can occur in patients without a significant travel history. Rhabdomyolysis as a complication has rarely been reported, and never in a child. A child with Salmonella enterica serovar Typhi septicemia, complicated by rhabdomyolysis, encephalopathy and pancreatitis is described and all 15 reported cases to date are summarized.

Typhoid fever: case report and literature review.

PubMed

Sanhueza Palma, Natalia Carolina; Farías Molina, Solange; Calzadilla Riveras, Jeannette; Hermoso, Amalia

2016-06-21

Typhoid fever remains a major health problem worldwide, in contrast to Chile, where this disease is an isolated finding. Clinical presentation is varied, mainly presenting with fever, malaise, abdominal discomfort, and nonspecific symptoms often confused with other causes of febrile syndrome. We report a six-year-old, male patient presenting with fever of two weeks associated with gastrointestinal symptoms, malaise, hepatomegaly and elevated liver enzymes. Differential diagnoses were considered and a Widal reaction and two blood cultures were requested; both came back positive, confirming the diagnosis of typhoid fever caused by Salmonella typhi. Prior to diagnosis confirmation, empirical treatment was initiated with ceftriaxone and metronidazole, with partial response; then drug therapy was adjusted according to ciprofloxacin susceptibility testing with a favorable clinical response. We discuss diagnostic methods and treatment of enteric fever with special emphasis on typhoid fever.

Typhoid fever cases in the U.S. military.

PubMed

Sorrell, Tia; Selig, Daniel J; Riddle, Mark S; Porter, Chad K

2015-10-14

Salmonella enterica, serovar Typhi (S. Typhi), a causative agent of enteric fever (typhoid fever), predominately affects populations in developing regions with poor access to clean food and water. In addition, travelers to these regions are at risk of exposure. We report the epidemiological characteristics of S. Typhi cases among active duty United States military personnel from 1998 to 2011 using data obtained from the Defense Medical Surveillance System. Cases were identified based on International Classification for Disease Ninth Edition - Clinical Modification codes. We identified a total of 205 cases S. Typhi for an incidence of 1.09 per 100,000 person-years. Cases were on average 31.7 years old, predominately married (n = 129, 62.9 %), Caucasian (n = 142, 69.3 %), male (n = 176, 85.9 %), and had a high school education (n = 101, 49.3 %). Of the identified cases, 122 had received a Typhoid vaccination within 4 years of diagnosis. This study provides an overview of enteric fever in the United States military. The incidence was similar to the general U.S. population except for increased incidence from 1998 to 2000, perhaps attributable to operational deployments in that period. Given that vaccination is an effective primary prevention measure against typhoid fever, active monitoring of pre-deployment vaccine history is warranted.

Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure

PubMed Central

Baker, Stephen; Duy, Pham Thanh; Nga, Tran Vu Thieu; Dung, Tran Thi Ngoc; Phat, Voong Vinh; Chau, Tran Thuy; Turner, A Keith; Farrar, Jeremy; Boni, Maciej F

2013-01-01

Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by the bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering treatment and control efforts. Using in vitro competition experiments, we assayed the fitness of eleven isogenic S. Typhi strains with resistance mutations in the FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out of 11 mutants carried a selective advantage over the antimicrobial-sensitive parent strain, indicating that FQ resistance in S. Typhi is not typically associated with fitness costs. Double-mutants exhibited higher than expected fitness as a result of synergistic epistasis, signifying that epistasis may be a critical factor in the evolution and molecular epidemiology of S. Typhi. Our findings have important implications for the management of drug-resistant S. Typhi, suggesting that FQ-resistant strains would be naturally maintained even if fluoroquinolone use were reduced. DOI: http://dx.doi.org/10.7554/eLife.01229.001 PMID:24327559

The Vi Capsular Polysaccharide Enables Salmonella enterica Serovar Typhi to Evade Microbe-Guided Neutrophil Chemotaxis

PubMed Central

Wangdi, Tamding; Lee, Cheng-Yuk; Spees, Alanna M.; Yu, Chenzhou; Kingsbury, Dawn D.; Winter, Sebastian E.; Hastey, Christine J.; Wilson, R. Paul

2014-01-01

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a disseminated infection, while the closely related pathogen S. enterica serovar Typhimurium (S. Typhimurium) is associated with a localized gastroenteritis in humans. Here we investigated whether both pathogens differ in the chemotactic response they induce in neutrophils using a single-cell experimental approach. Surprisingly, neutrophils extended chemotactic pseudopodia toward Escherichia coli and S. Typhimurium, but not toward S. Typhi. Bacterial-guided chemotaxis was dependent on the presence of complement component 5a (C5a) and C5a receptor (C5aR). Deletion of S. Typhi capsule biosynthesis genes markedly enhanced the chemotactic response of neutrophils in vitro. Furthermore, deletion of capsule biosynthesis genes heightened the association of S. Typhi with neutrophils in vivo through a C5aR-dependent mechanism. Collectively, these data suggest that expression of the virulence-associated (Vi) capsular polysaccharide of S. Typhi obstructs bacterial-guided neutrophil chemotaxis. PMID:25101794

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

PubMed

Lutterloh, Emily; Likaka, Andrew; Sejvar, James; Manda, Robert; Naiene, Jeremias; Monroe, Stephan S; Khaila, Tadala; Chilima, Benson; Mallewa, Macpherson; Kampondeni, Sam D; Lowther, Sara A; Capewell, Linda; Date, Kashmira; Townes, David; Redwood, Yanique; Schier, Joshua G; Nygren, Benjamin; Tippett Barr, Beth; Demby, Austin; Phiri, Abel; Lungu, Rudia; Kaphiyo, James; Humphrys, Michael; Talkington, Deborah; Joyce, Kevin; Stockman, Lauren J; Armstrong, Gregory L; Mintz, Eric

2012-04-01

Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Typhoid fever in young children in Bangladesh: clinical findings, antibiotic susceptibility pattern and immune responses.

PubMed

Khanam, Farhana; Sayeed, Md Abu; Choudhury, Feroza Kaneez; Sheikh, Alaullah; Ahmed, Dilruba; Goswami, Doli; Hossain, Md Lokman; Brooks, Abdullah; Calderwood, Stephen B; Charles, Richelle C; Cravioto, Alejandro; Ryan, Edward T; Qadri, Firdausi

2015-04-01

Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains. As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults. We similarly assessed membrane preparation (MP) IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years) with those seen in older children (6-17 years), adults (18-59 years), and age-matched healthy controls. We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid. This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest can be used as marker of recent typhoid fever, even in young children.

Bottled beverages and typhoid fever: the Mexican epidemic of 1972-73.

PubMed Central

Gonzalez-Cortes, A; Gangarosa, E J; Parrilla, C; Martin, W T; Espinosa-Ayala, A M; Ruiz, L; Bessudo, D; Hernandez-Arreortua, H

1982-01-01

A chloramphenicol resistant strain of S. typhi which caused a very large epidemic of typhoid fever in Mexico in 1972-73 survived in opened bottles of one carbonated drink with a pH of 4.6 for two weeks and in another such drink with a pH of 5.1 for six months. Bottled beverages are potential sources of large outbreaks of enteric disease, and deserve the same type of standards sand monitoring as comparable fluids such as milk. PMID:7091481

Diagnosis of imported Ugandan typhoid fever based on local outbreak information: A case report.

PubMed

Ota, Shinichiro; Maki, Yohei; Mori, Kazuma; Hamamoto, Takaaki; Kurokawa, Atsushi; Ishihara, Masashi; Yamamoto, Takayuki; Imai, Kazuo; Misawa, Kazuhisa; Yuki, Atsushi; Fujikura, Yuji; Maeda, Takuya; Kawana, Akihiko

2016-11-01

Re-emerging multidrug-resistant typhoid fever is becoming a worldwide threat, especially in East Africa. At the beginning of 2015, an outbreak of typhoid fever started in the capital city of Uganda, and 1940 suspected cases were reported by 5 March 2015. In this report, we describe a case of typhoid fever caused by a MDR strain with HIV infection and hemoglobin S-syndrome thalassemia in an Ugandan from Kampala City. It is essential to consider MDR strains of Salmonella enterica serovar Typhi infections, including fluoroquinolone-resistant strains, in patients from Africa and Southeast Asia. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Salmonella Typhi genomics: envisaging the future of typhoid eradication.

PubMed

Yap, Kien-Pong; Thong, Kwai Lin

2017-08-01

Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development. © 2017 John Wiley & Sons Ltd.

Role of Environmental Factors in Shaping Spatial Distribution of Salmonella enterica Serovar Typhi, Fiji

PubMed Central

Watson, Conall; Nikolay, Birgit; Lowry, John H.; Thieu, Nga Tran Vu; Van, Tan Trinh; Ngoc, Dung Tran Thi; Rawalai, Kitione; Taufa, Mere; Coriakula, Jerimaia; Lau, Colleen L.; Nilles, Eric J.; Edmunds, W. John; Kama, Mike; Baker, Stephen; Cano, Jorge

2018-01-01

Fiji recently experienced a sharp increase in reported typhoid fever cases. To investigate geographic distribution and environmental risk factors associated with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional cluster survey with associated serologic testing for Vi capsular antigen–specific antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots with high seroprevalence of Vi-specific antibodies were identified in northeastern mainland Fiji. Risk for Vi seropositivity increased with increased annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12–1.42), and decreased with increased distance from major rivers and creeks (OR 0.89/km increase, 95% CI 0.80–0.99) and distance to modeled flood-risk areas (OR 0.80/quintile increase, 95% CI 0.69–0.92) after being adjusted for age, typhoid fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi and its spatial distribution in Fiji are driven by environmental factors. Our findings can directly affect typhoid fever control efforts in Fiji. PMID:29350150

Immunoblot detection of class-specific humoral immune response to outer membrane proteins isolated from Salmonella typhi in humans with typhoid fever.

PubMed Central

Ortiz, V; Isibasi, A; García-Ortigoza, E; Kumate, J

1989-01-01

The studies reported here were undertaken to assess the ability of the outer membrane proteins (OMPs) of Salmonella typhi to induce a humoral immune response in humans with typhoid fever. OMPs were isolated with the nonionic detergent Triton X-100 and were found to be contaminated with approximately 4% lipopolysaccharide. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns showed protein bands with molecular size ranges from 17 to 70 kilodaltons; the major groups of proteins were those that correspond to the porins and OmpA of gram-negative bacteria. Rabbit antiserum to OMPs or to S. typhi recognized OMPs after absorption with lipopolysaccharide. Sera from patients with typhoid fever contained immunoglobulin M antibodies which reacted with a protein of 28 kilodaltons and immunoglobulin G antibodies which reacted mainly with the porins, as determined by immunoblotting. These results indicate that the porins are the major immunogenic OMPs from S. typhi and that the immune response induced in the infection could be related to the protective status. Images PMID:2768450

Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.

PubMed

Blohmke, Christoph J; Darton, Thomas C; Jones, Claire; Suarez, Nicolas M; Waddington, Claire S; Angus, Brian; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Kane, Leanne; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Duque-Correa, Maria A; Wright, James C; Roumeliotis, Theodoros I; Yu, Lu; Choudhary, Jyoti S; Mejias, Asuncion; Ramilo, Octavio; Shanyinde, Milensu; Sztein, Marcelo B; Kingsley, Robert A; Lockhart, Stephen; Levine, Myron M; Lynn, David J; Dougan, Gordon; Pollard, Andrew J

2016-05-30

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host-pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. © 2016 Blohmke et al.

Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever

PubMed Central

Jones, Claire; Waddington, Claire S.; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Roumeliotis, Theodoros I.; Yu, Lu; Ramilo, Octavio; Sztein, Marcelo B.; Kingsley, Robert A.; Levine, Myron M.

2016-01-01

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. PMID:27217537

Enhanced detection rate of typhoid fever among clinically suspected patients in a tertiary referral hospital in Dhaka, Bangladesh using nested polymerase chain reaction technology.

PubMed

Khan, S; Miah, M R; Khatun, S

2015-12-01

A nested polymerase chain reaction (PCR) specific for Salmonella enterica subspecies enteric serovar Typhi was used for the detection of the pathogen, in blood. This study was done during the period of March 2013 to February 2014. A total of 80 clinically suspected cases of typhoid fever were included in the study. Blood was collected from all participating individuals. Nested PCR targeting the flagellin gene (fliC) of Salmonella Typhi & blood culture were done for each of the cases. The positivity rate of PCR & blood culture was 70%& 20% respectively. The positivity rate of PCR was significantly higher than blood culture (P< 0.05). With the nested PCR, S. Typhi DNAs were detected from blood specimens of 67.2% (43/64) patients among the suspected typhoid fever cases on the basis of clinical features but with negative cultures. We conclude that the PCR technique could be used as a novel diagnostic method of typhoid fever, particularly in culture-negative cases in an endemic country like Bangladesh.

The Gathering Storm: Is Untreatable Typhoid Fever on the Way?

PubMed Central

Simon, Raphael

2018-01-01

ABSTRACT Klemm et al. (mBio 9:e00105-18, 2018, https://doi.org/10.1128/mBio.00105-18) present comprehensive antibiotic sensitivity patterns and genomic sequence data on Salmonella enterica serovar Typhi blood culture isolates from typhoid fever cases during an epidemic in Pakistan. Microbiologic and genomic data pinpoint the identities and locations of the antimicrobial resistance genes and the outbreak strain’s lineage. They propose that Salmonella enterica serovar Typhi be added to the list of bacterial pathogens of public health importance that have become extensively drug resistant (XDR). This paper portends possible dire scenarios for typhoid fever control if XDR strains disseminate globally. Since the outbreak strain is of the H58 haplotype, known for its ability to spread worldwide and displace endemic S. Typhi, this concern is well-founded. The report of Klemm et al. forewarns the global community to address control of typhoid fever more aggressively through prevention, should therapeutic options disappear. This Commentary frames the Klemm et al. findings within a historic perspective. PMID:29559573

What proportion of Salmonella Typhi cases are detected by blood culture? A systematic literature review.

PubMed

Mogasale, Vittal; Ramani, Enusa; Mogasale, Vijayalaxmi V; Park, JuYeon

2016-05-17

Blood culture is often used in definitive diagnosis of typhoid fever while, bone marrow culture has a greater sensitivity and considered reference standard. The sensitivity of blood culture measured against bone marrow culture results in measurement bias because both tests are not fully sensitive. Here we propose a combination of the two cultures as a reference to define true positive S. Typhi cases. Based on a systematic literature review, we identified ten papers that had performed blood and bone marrow culture for S. Typhi in same subjects. We estimated the weighted mean of proportion of cases detected by culture measured against true S. Typhi positive cases using a random effects model. Of 529 true positive S. Typhi cases, 61 % (95 % CI 52-70 %) and 96 % (95 % CI 93-99 %) were detected by blood and bone marrow cultures respectively. Blood culture sensitivity was 66 % (95 % CI 56-75 %) when compared with bone marrow culture results. The use of blood culture sensitivity as a proxy measure to estimate the proportion of typhoid fever cases detected by blood culture is likely to be an underestimate. As blood culture sensitivity is used as a correction factor in estimating typhoid disease burden, epidemiologists and policy makers should account for the underestimation.

Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

PubMed

Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Magder, Laurence S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

2016-06-01

A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

Another typhoid patient from Japan.

PubMed

Thapa, Rachana; Banskota, Nalin; Pokharel, Jhapindra; Subedi, Bishnu H; Basnyat, Buddha

2010-01-01

Typhoid treatment was empirically started in a Japanese patient with undifferentiated fever in Nepal since Japanese tourists, unlike most Americans and Europeans to South Asia, are unable to obtain typhoid vaccination in Japan even for travel to this area of high endemicity. Subsequently, his blood culture grew out Salmonella typhi.

Salmonella Infections in Childhood.

PubMed

Bula-Rudas, Fernando J; Rathore, Mobeen H; Maraqa, Nizar F

2015-08-01

Salmonella are gram-negative bacilli within the family Enterobacteriaceae. They are the cause of significant morbidity and mortality worldwide. Animals (pets) are an important reservoir for nontyphoidal Salmonella, whereas humans are the only natural host and reservoir for Salmonella Typhi. Salmonella infections are a major cause of gastroenteritis worldwide. They account for an estimated 2.8 billion cases of diarrheal disease each year. The transmission of Salmonella is frequently associated with the consumption of contaminated water and food of animal origin, and it is facilitated by conditions of poor hygiene. Nontyphoidal Salmonella infections have a worldwide distribution, whereas most typhoidal Salmonella infections in the United States are acquired abroad. In the United States, Salmonella is a common agent for food-borne–associated infections. Several outbreaks have been identified and are most commonly associated with agricultural products. Nontyphoidal Salmonella infection is usually characterized by a self-limited gastroenteritis in immunocompetent hosts in industrialized countries, but it may also cause invasive disease in vulnerable individuals (eg, children less than 1 year of age, immunocompromised). Antibiotic treatment is not recommended for treatment of mild to moderate gastroenteritis by nontyphoidal Salmonella in immunocompetent adults or children more than 1 year of age. Antibiotic treatment is recommended for nontyphoidal Salmonella infections in infants less than 3 months of age, because they are at higher risk for bacteremia and extraintestinal complications. Typhoid (enteric) fever and its potential complications have a significant impact on children, especially those who live in developing countries. Antibiotic treatment of typhoid fever has become challenging because of the emergence of Salmonella Typhi strains that are resistant to classically used first-line agents: ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol. The choice of antibiotics for the management of typhoid fever should be guided by the local resistance pattern. Recommendations include using an extended spectrum cephalosporin, azithromycin, or a fluoroquinolone. Fecal carriage of Salmonella is an important factor in the spread of the organism to healthy individuals. The most important measures to prevent the spread and outbreaks of Salmonella infections and typhoid fever are adequate sanitation protocols for food processing and handling as well as hand hygiene. In the United States, 2 vaccines are commercially available against Salmonella Typhi. The WHO recommends the use of these vaccines in endemic areas and for outbreak control.

Typhoid outbreak investigation in Dzivaresekwa, suburb of Harare City, Zimbabwe, 2011.

PubMed

Muti, Monica; Gombe, Notion; Tshimanga, Mufuta; Takundwa, Lucia; Bangure, Donewell; Mungofa, Stanley; Chonzi, Prosper

2014-01-01

Typhoid fever is a systemic infection caused by a Gram negative bacterium, Salmonella typhi. Harare City reported 1078 cases of suspected typhoid fever cases from October 2011 to January 2012. We initiated an investigation to identify possible source of transmission so as to institute control measures. An unmatched 1:1 case-control study was conducted. A questionnaire was administered to study participants to identify risk factors for contracting typhoid. A case was a resident of Dzivaresekwa who presented with signs and symptoms of typhoid between October and December 2011. Water samples were collected for microbiological analysis. 115 cases and 115 controls were enrolled. Drinking water from a well (OR=6.2 95% CI (2.01-18.7)), attending a gathering (OR=11.3 95% CI (4.3-29.95)), boiling drinking water (OR=0.21 95% CI (0.06-0.76)) and burst sewer pipe at home (OR=1.19 95% CI (0.67-2.14)) were factors associated with contracting typhoid. Independent risk factors for contracting typhoid were drinking water from a well (AOR=5.8; 95% CI (1.90-17.78)), and burst sewer pipe at home (AOR=1.20; 95% CI (1.10-2.19)). Faecal coli forms and E. coli were isolated from 8/8 well water samples. Stool, urine and blood specimens were cultured and serotyped for Salmonella typhi and 24 cases were confirmed positive. Shigella, Giardia and E coli were also isolated. Ciprofloxacin, X-pen and Rocephin were used for case management. No complications were reported. Contaminated water from unprotected water sources was the probable source of the outbreak. Harare City Engineer must invest in repairing water and sewage reticulation systems in the city.

Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid.

PubMed

McClelland, Michael; Sanderson, Kenneth E; Clifton, Sandra W; Latreille, Phil; Porwollik, Steffen; Sabo, Aniko; Meyer, Rekha; Bieri, Tamberlyn; Ozersky, Phil; McLellan, Michael; Harkins, C Richard; Wang, Chunyan; Nguyen, Christine; Berghoff, Amy; Elliott, Glendoria; Kohlberg, Sara; Strong, Cindy; Du, Feiyu; Carter, Jason; Kremizki, Colin; Layman, Dan; Leonard, Shawn; Sun, Hui; Fulton, Lucinda; Nash, William; Miner, Tracie; Minx, Patrick; Delehaunty, Kim; Fronick, Catrina; Magrini, Vincent; Nhan, Michael; Warren, Wesley; Florea, Liliana; Spieth, John; Wilson, Richard K

2004-12-01

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

PubMed

Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

2017-09-12

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol

PubMed Central

Alvarez, Monica I.; Glover, Luke C.; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H.; Walton, Eric M.; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I.; McClean, Colleen M.; Chinh, Nguyen Tran; Medina, Marisa W.; Dunstan, Sarah J.

2017-01-01

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi (S. Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S. Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches. PMID:28827342

Use of a novel antigen expressing system to study the Salmonella enterica serovar Typhi protein recognition by T cells

PubMed Central

Lou, David; Steiner, Stephanie; Rezwanul, Tasmia; Guo, Qin; Picking, William D.; Nene, Vishvanath; Sztein, Marcelo B.

2017-01-01

Salmonella enterica serovar Typhi (S. Typhi), the causative agent of the typhoid fever, is a pathogen of great public health importance. Typhoid vaccines have the potential to be cost-effective measures towards combating this disease, yet the antigens triggering host protective immune responses are largely unknown. Given the key role of cellular-mediated immunity in S. Typhi protection, it is crucial to identify S. Typhi proteins involved in T-cell responses. Here, cells from individuals immunized with Ty21a typhoid vaccine were collected before and after immunization and used as effectors. We also used an innovative antigen expressing system based on the infection of B-cells with recombinant Escherichia coli (E. coli) expressing one of four S. Typhi gene products (i.e., SifA, OmpC, FliC, GroEL) as targets. Using flow cytometry, we found that the pattern of response to specific S. Typhi proteins was variable. Some individuals responded to all four proteins while others responded to only one or two proteins. We next evaluated whether T-cells responding to recombinant E. coli also possess the ability to respond to purified proteins. We observed that CD4+ cell responses, but not CD8+ cell responses, to recombinant E. coli were significantly associated with the responses to purified proteins. Thus, our results demonstrate the feasibility of using an E. coli expressing system to uncover the antigen specificity of T-cells and highlight its applicability to vaccine studies. These results also emphasize the importance of selecting the stimuli appropriately when evaluating CD4+ and CD8+ cell responses. PMID:28873442

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

PubMed

Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Waddington, Claire S; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A; Jeppesen, Catherine A; Moore, Maria; Thompson, Ben A V; John, Tessa; Kingsley, Robert A; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2016-08-01

Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge. ClinicalTrials.gov (NCT01405521) and EudraCT (number 2011-000381-35).

Molecular diagnosis of Salmonella typhi and its virulence in suspected typhoid blood samples through nested multiplex PCR.

PubMed

Prabagaran, Solai Ramatchandirane; Kalaiselvi, Vellingiri; Chandramouleeswaran, Naganathan; Deepthi, Krishnan Nair Geetha; Brahmadathan, Kootallur Narayanan; Mani, Mariappa

2017-08-01

A nested multiplex polymerase chain reaction (PCR) based diagnosis was developed for the detection of virulent Salmonella typhi in the blood specimens from patients suspected for typhoid fever. After the Widal test, two pairs of primers were used for the detection of flagellin gene (fliC) of S. typhi. Among them, those positive for fliC alone were subjected to identification of genes in Via B operon of Salmonella Pathogenesity Island (SPI-7) where four primer pairs were used to detect tviA and tviB genes. Among 250 blood samples tested, 115 were positive by fliC PCR; 22 of these were negative for tviA and tviB. Hence, the method described here can be used to diagnose the incidence of Vi-negative serovar typhi especially in endemic regions where the Vi vaccine is administered. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of serological diagnostic tests for typhoid fever in Papua New Guinea using a composite reference standard.

PubMed

Siba, Valentine; Horwood, Paul F; Vanuga, Kilagi; Wapling, Johanna; Sehuko, Rebecca; Siba, Peter M; Greenhill, Andrew R

2012-11-01

Typhoid fever remains a major global health problem. A major impediment to improving outcomes is the lack of appropriate diagnostic tools, which have not significantly improved in low-income settings for 100 years. We evaluated two commercially available rapid diagnostic tests (Tubex and TyphiDot), a prototype (TyphiRapid TR-02), and the commonly used single-serum Widal test in a previously reported high-burden area of Papua New Guinea. Samples were collected from 530 outpatients with axillary temperatures of ≥37.5°C, and analysis was conducted on all malaria-negative samples (n = 500). A composite reference standard of blood culture and PCR was used, by which 47 participants (9.4%) were considered typhoid fever positive. The sensitivity and specificity of the Tubex (51.1% and 88.3%, respectively) and TyphiDot (70.0% and 80.1%, respectively) tests were not high enough to warrant their ongoing use in this setting; however, the sensitivity and specificity for the TR-02 prototype were promising (89.4% and 85.0%, respectively). An axillary temperature of ≥38.5°C correlated with typhoid fever (P = 0.014). With an appropriate diagnostic test, conducting typhoid fever diagnosis only on patients with high-grade fever could dramatically decrease the costs associated with diagnosis while having no detrimental impact on the ability to accurately diagnose the illness.

Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type Salmonella enterica Serovar Typhi

PubMed Central

Zhang, Yan; Brady, Arthur; Jones, Cheron; Song, Yang; Darton, Thomas C.; Jones, Claire; Blohmke, Christoph J.; Pollard, Andrew J.; Magder, Laurence S.; Fasano, Alessio; Sztein, Marcelo B.

2018-01-01

ABSTRACT Insights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-type Salmonella enterica serovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota. Metatranscriptome analysis of longitudinal stool samples collected from study subjects revealed two stable patterns of gene expression for the human gut microbiota, dominated by transcripts from either Methanobrevibacter or a diverse representation of genera in the Firmicutes phylum. Immunization with one of two live oral attenuated vaccines against S. Typhi had minimal effects on the composition or function of the gut microbiota. It was observed that subjects harboring the methanogen-dominated transcriptome community at baseline displayed a lower risk of developing symptoms of typhoid following challenge with wild-type S. Typhi. Furthermore, genes encoding antioxidant proteins, metal homeostasis and transport proteins, and heat shock proteins were expressed at a higher level at baseline or after challenge with S. Typhi in subjects who did not develop symptoms of typhoid. These data suggest that functional differences relating to redox potential and ion homeostasis in the gut microbiota may impact clinical outcomes following exposure to wild-type S. Typhi. PMID:29739901

Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial.

PubMed

Jin, Celina; Gibani, Malick M; Moore, Maria; Juel, Helene B; Jones, Elizabeth; Meiring, James; Harris, Victoria; Gardner, Jonathan; Nebykova, Anna; Kerridge, Simon A; Hill, Jennifer; Thomaides-Brears, Helena; Blohmke, Christoph J; Yu, Ly-Mee; Angus, Brian; Pollard, Andrew J

2017-12-02

Salmonella enterica serovar Typhi (S Typhi) is responsible for an estimated 20 million infections and 200 000 deaths each year in resource poor regions of the world. Capsular Vi-polysaccharide-protein conjugate vaccines (Vi-conjugate vaccines) are immunogenic and can be used from infancy but there are no efficacy data for the leading candidate vaccine being considered for widespread use. To address this knowledge gap, we assessed the efficacy of a Vi-tetanus toxoid conjugate vaccine using an established human infection model of S Typhi. In this single-centre, randomised controlled, phase 2b study, using an established outpatient-based human typhoid infection model, we recruited healthy adult volunteers aged between 18 and 60 years, with no previous history of typhoid vaccination, infection, or prolonged residency in a typhoid-endemic region. Participants were randomly assigned (1:1:1) to receive a single dose of Vi-conjugate (Vi-TT), Vi-polysaccharide (Vi-PS), or control meningococcal vaccine with a computer-generated randomisation schedule (block size 6). Investigators and participants were masked to treatment allocation, and an unmasked team of nurses administered the vaccines. Following oral ingestion of S Typhi, participants were assessed with daily blood culture over a 2-week period and diagnosed with typhoid infection when meeting pre-defined criteria. The primary endpoint was the proportion of participants diagnosed with typhoid infection (ie, attack rate), defined as persistent fever of 38°C or higher for 12 h or longer or S Typhi bacteraemia, following oral challenge administered 1 month after Vi-vaccination (Vi-TT or Vi-PS) compared with control vaccination. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT02324751, and is ongoing. Between Aug 18, 2015, and Nov 4, 2016, 112 participants were enrolled and randomly assigned; 34 to the control group, 37 to the Vi-PS group, and 41 to the Vi-TT group. 103 participants completed challenge (31 in the control group, 35 in the Vi-PS group, and 37 in the Vi-TT group) and were included in the per-protocol population. The composite criteria for typhoid diagnosis was met in 24 (77%) of 31 participants in the control group, 13 (35%) of 37 participants in the Vi-TT group, and 13 (35%) of 35 participants in the Vi-PS group to give vaccine efficacies of 54·6% (95% CI 26·8-71·8) for Vi-TT and 52·0% (23·2-70·0) for Vi-PS. Seroconversion was 100% in Vi-TT and 88·6% in Vi-PS participants, with significantly higher geometric mean titres detected 1-month post-vaccination in Vi-TT vaccinees. Four serious adverse events were reported during the conduct of the study, none of which were related to vaccination (one in the Vi-TT group and three in the Vi-PS group). Vi-TT is a highly immunogenic vaccine that significantly reduces typhoid fever cases when assessed using a stringent controlled model of typhoid infection. Vi-TT use has the potential to reduce both the burden of typhoid fever and associated health inequality. The Bill & Melinda Gates Foundation and the European Commission FP7 grant, Advanced Immunization Technologies (ADITEC). Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study.

PubMed

Marks, Florian; von Kalckreuth, Vera; Aaby, Peter; Adu-Sarkodie, Yaw; El Tayeb, Muna Ahmed; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Biggs, Holly M; Bjerregaard-Andersen, Morten; Breiman, Robert F; Campbell, James I; Cosmas, Leonard; Crump, John A; Espinoza, Ligia Maria Cruz; Deerin, Jessica Fung; Dekker, Denise Myriam; Fields, Barry S; Gasmelseed, Nagla; Hertz, Julian T; Van Minh Hoang, Nguyen; Im, Justin; Jaeger, Anna; Jeon, Hyon Jin; Kabore, Leon Parfait; Keddy, Karen H; Konings, Frank; Krumkamp, Ralf; Ley, Benedikt; Løfberg, Sandra Valborg; May, Jürgen; Meyer, Christian G; Mintz, Eric D; Montgomery, Joel M; Niang, Aissatou Ahmet; Nichols, Chelsea; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Jin Kyung; Park, Se Eun; Rabezanahary, Henintsoa; Rakotozandrindrainy, Raphaël; Raminosoa, Tiana Mirana; Razafindrabe, Tsiriniaina Jean Luco; Sampo, Emmanuel; Schütt-Gerowitt, Heidi; Sow, Amy Gassama; Sarpong, Nimako; Seo, Hye Jin; Sooka, Arvinda; Soura, Abdramane Bassiahi; Tall, Adama; Teferi, Mekonnen; Thriemer, Kamala; Warren, Michelle R; Yeshitela, Biruk; Clemens, John D; Wierzba, Thomas F

2017-03-01

Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0-0) in Sudan to 383 (274-535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178-316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG against Hemolysin E and Lipopolysaccharide

PubMed Central

Huw Davies, D.; Jain, Aarti; Nakajima, Rie; Liang, Li; Jasinskis, Algis; Supnet, Medalyn; Felgner, Philip L.; Teng, Andy; Pablo, Jozelyn; Molina, Douglas M.; Obaro, Stephen K.

2016-01-01

Inexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (∼500 seropositive antigens) and mainly low level, with a small number of stronger “hits,” whereas the profile in U.S. adults was < 1/5 as broad, consistent with endemic exposure in Nigeria. Nigerian profiles were largely unaffected by clinical diagnosis, although the response against t1477 (hemolysin E) consistently emerged as stronger in typhoid cases. The response to LPS was also a strong discriminator of healthy controls and typhoid, although LPS did not discriminate between typhoid and nontyphoidal Salmonella (NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease. PMID:27215295

[Epidemiological characteristics of typhoid fever and antibiotic susceptibility testing of Salmonella Typhi isolates in Guangxi, 1994-2013].

PubMed

Wang, Mingliu; Kan, Biao; Yang, Jin; Lin, Mei; Yan, Meiying; Zeng, Jun; Quan, Yi; Liao, Hezhuang; Zhou, Lingyun; Jiang, Zhenling; Huang, Dehui

2014-08-01

Through analyzing the typhoid epidemics and to determine and monitor regional resistance characteristics of the shift of drug resistant profile on Salmonella (S.) Typhi, to understand the related epidemiological characteristics of typhoid fever and to provide evidence for the development of strategies, in Guangxi. Data of typhoid fever from surveillance and reporting system between 1994 to 2013 was collected and statistically analyzed epidemiologically. The susceptibility of 475 S. Typhi isolates from patients on ten antibiotics was tested by broth micro-dilution method and minimum inhibition concentration was obtained and interpreted based on the CLSI standard. From 1994 to 2013, a total of 57 928 cases of typhoid fever were reported in Guangxi province with an annual incidence of 6.29/100 000 and mortality as 0.03%. The higher incidence was observed in the population under 20 years of age. There was no significant difference on incidence between male and female, but farmers and students were among the hardest hit groups. More cases were seen from the northern part of the province. Cases appeared all year round with the peak from May to October. A total of 13 major outbreaks during 2001 to 2013 were reported and the main transmission route was water-borne. All the strains were sensitive to third generation cephalosporins cefotaxime and fluoroquinolones norfloxacin. The susceptibility rates to tetracycline, chloramphenicol, ampicillin and gentamicin was around 98% but relative lower susceptible rate to ciprofloxacin was seen as 89.89% . The lowest susceptibility was found for streptomycin and sulfamethoxazole agents, with the rates as 67.73% and 65.89% , respectively. One strain was found to have been resistant to ciprofloxacin and another 47 isolates with reduced susceptibility to ciprofloxacin. Twenty eight isolates were found to be resistant to multiple antibiotics and one displayed ampicillin, chloramphenicol, streptomycin, sulfamethoxazole tetracycline and nalidixic acid (ACSSxT-NAL) resistance profile. This was the first report in China. Multi-drug resistant strains were frequently isolated from small scale outbreaks of typhoid fever. The incidence of typhoid fever in Guangxi was still high and some strains showed multi-drug resistance and reduced susceptibility to ciprofloxacin, indicating that the surveillance and monitor programs on drug resistance of S. Typhi should be strengthened, to prevent large scale outbreaks of typhoid fever in this province.

The unrecognized burden of typhoid fever.

PubMed

Obaro, Stephen K; Iroh Tam, Pui-Ying; Mintz, Eric Daniel

2017-03-01

Typhoid fever (TF), caused by Salmonella enterica serovar Typhi, is the most common cause of enteric fever, responsible for an estimated 129,000 deaths and more than 11 million cases annually. Although several reviews have provided global and regional TF disease burden estimates, major gaps in our understanding of TF epidemiology remain. Areas covered: We provide an overview of the gaps in current estimates of TF disease burden and offer suggestions for addressing them, so that affected communities can receive the full potential of disease prevention offered by vaccination and water, sanitation, and hygiene interventions. Expert commentary: Current disease burden estimates for TF do not capture cases from certain host populations, nor those with atypical presentations of TF, which may lead to substantial underestimation of TF cases and deaths. These knowledge gaps pose major obstacles to the informed use of current and new generation typhoid vaccines.

Biomagnetic Pair Therapy and Typhoid Fever: A Pilot Study.

PubMed

Frank, Bryan L

2017-10-01

Objective: This pilot study examined the laboratory responses of patients with laboratory-documented typhoid fever who were treated with Biomagnetic Pair Therapy (BPT; medical biomagnetism), a specific application of pairs of magnets for various ailments that are infectious and otherwise. Materials and Methods: This study was an assessment of patients' response to treatment with only BPT for Salmonella typhi infections (typhoid fever) using standard conventional laboratory techniques. The research was conducted in an outpatient village clinic in Kenya. There were 52 participants who were evaluated for possible systemic illness, including typhoid fever, from an open-label study. Participants who felt sick and requested testing for possible typhoid fever were tested with a standard Widal test by a certified laboratory technician. Participants who tested positive (13 patients) were then treated with BPT (a "First Aid" approach) only. These participants then returned for follow-up laboratory and clinical evaluations after 2 days. Results: Most of the participants (10 of 13) retested as negative, and all patients reported symptomatic clinical improvement. Conclusions: As a significant majority of participants demonstrated clearing of their S. typhi after BPT, this technique should be studied further in larger trials for its efficacy in treating typhoid fever.

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide.

PubMed

Davies, D Huw; Jain, Aarti; Nakajima, Rie; Liang, Li; Jasinskis, Algis; Supnet, Medalyn; Felgner, Philip L; Teng, Andy; Pablo, Jozelyn; Molina, Douglas M; Obaro, Stephen K

2016-08-03

Inexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (∼500 seropositive antigens) and mainly low level, with a small number of stronger "hits," whereas the profile in U.S. adults was < 1/5 as broad, consistent with endemic exposure in Nigeria. Nigerian profiles were largely unaffected by clinical diagnosis, although the response against t1477 (hemolysin E) consistently emerged as stronger in typhoid cases. The response to LPS was also a strong discriminator of healthy controls and typhoid, although LPS did not discriminate between typhoid and nontyphoidal Salmonella (NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease. © The American Society of Tropical Medicine and Hygiene.

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

PubMed Central

Jones, Claire; Blohmke, Christoph J.; Waddington, Claire S.; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A.; Jeppesen, Catherine A.; Moore, Maria; Thompson, Ben A. V.; John, Tessa; Kingsley, Robert A.; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B.; Dougan, Gordon; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.

2016-01-01

Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Conclusions Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge. Trial registration ClinicalTrials.gov (NCT01405521) and EudraCT (number 2011-000381-35). PMID:27533046

Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans

PubMed Central

Darton, Thomas C.; Blohmke, Christoph J.; Giannoulatou, Eleni; Waddington, Claire S.; Jones, Claire; Sturges, Pamela; Webster, Craig; Drakesmith, Hal; Pollard, Andrew J.; Armitage, Andrew E.

2015-01-01

Background Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/Principal Findings Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/Significance We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi. PMID:26394303

An Outbreak of Food-Borne Typhoid Fever Due to Salmonella enterica Serotype Typhi in Japan Reported for the First Time in 16 Years

PubMed Central

Kobayashi, Tetsuro; Kutsuna, Satoshi; Hayakawa, Kayoko; Kato, Yasuyuki; Ohmagari, Norio; Uryu, Hideko; Yamada, Ritsuko; Kashiwa, Naoyuki; Nei, Takahito; Ehara, Akihito; Takei, Reiko; Mori, Nobuaki; Yamada, Yasuhiro; Hayasaka, Tomomi; Kagawa, Narito; Sugawara, Momoko; Suzaki, Ai; Takahashi, Yuno; Nishiyama, Hiroyuki; Morita, Masatomo; Izumiya, Hidemasa; Ohnishi, Makoto

2016-01-01

For the first time in 16 years, a food-borne outbreak of typhoid fever due to Salmonella enterica serotype Typhi was reported in Japan. Seven patients consumed food in an Indian buffet at a restaurant in the center of Tokyo, while one was a Nepali chef in the restaurant, an asymptomatic carrier and the implicated source of this outbreak. The multiple-locus variable-number tandem repeat analysis showed 100% consistency in the genomic sequence for five of the eight cases. PMID:26621565

78 FR 9399 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-08

... introduced into the licensed typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and was... combination typhoid-shigellosis oral vaccine. For collaboration opportunities, please contact Dr. Dennis J... gene region into a bacterial chromosome. Bacillary dysentery and enteric fevers continue to be...

Synergistic antimicrobial effect of nisin and p-cymene on Salmonella enterica serovar Typhi in vitro and on ready-to-eat food.

PubMed

Rattanachaikunsopon, Pongsak; Phumkhachorn, Parichat

2010-01-01

Foods contaminated with Salmonella enterica serovar Typhi are a major cause of typhoid fever, leading to public health problems and economic losses worldwide. Nisin and rho-cymene were tested in this study for their antimicrobial activity against S. Typhi at 4 degrees C and 37 degrees C. Nisin and rho-cymene, when used separately, did not inhibit the bacterium at either temperature. A synergistic antimicrobial effect between both compounds was observed when they were used simultaneously. This synergism was greater at 37 degrees C than at 4 degrees C. The lowest concentrations of nisin and rho-cymene required for complete inhibition of S. Typhi at 37 degrees C were 0.3 ppm and 1.5 ppm, respectively, and 0.3 ppm and 2.5 ppm at 4 degrees C. The potential of nisin and rho-cymene to control an S. Typhi population on ready-to-eat Thai-style pork sausage was also examined. The compounds were able to eliminate the contaminating bacterium with concentrations depending on the bacterial cell number on the food.

Comparison between DOT EIA IgM and Widal Test as early diagnosis of typhoid fever.

PubMed

Begum, Z; Hossain, M A; Musa, A K; Shamsuzzaman, A K; Mahmud, M C; Ahsan, M M; Sumona, A A; Ahmed, S; Jahan, N A; Alam, M; Begum, A

2009-01-01

A recently developed DOT enzyme immunoassay known as "Typhidot" for detecting IgM antibody against 50 KDa OMP antigen of Salmonella typhi, was evaluated on 100 clinically suspected typhoid fever cases and 40 age-sex matched controls, in the Department of Microbiology, Mymensingh Medical College during, the period from June 2006 to July 2007. Blood culture, Widal test, and DOT EIA for IgM test were performed in all patients. Among 100 clinically suspected typhoid fever cases, 35 were subsequently confirmed on the basis of positive blood culture for S. typhi and/or significant rising titre of Widal test. The DOT EIA IgM test could produce results within 1 hour. The result of the DOT EIA IgM test showed a good diagnostic value for typhoid fever. The sensitivity, specificity, positive and negative predictive value of the test was found as 91.42%, 90.00%, 88.88% and 92.30% respectively. On the other hand corresponding values for Widal test were of 42.85%, 85.00%, 71.42% and 62.96% respectively. Thus, The DOT EIA IgM seems to be a practical alternative to Widal test for early diagnosis of typhoid fever.

Desirability for a typhoid fever vaccine among rural residents, Pemba Island, Tanzania.

PubMed

Kaljee, Linda M; Pach, Alfred; Thriemer, Kamala; Ley, Benedikt; Jiddawi, Mohamed; Puri, Mahesh; Ochiai, Leon; Wierzba, Thomas; Clemens, John; Ali, Said M

2013-06-24

Surveillance data indicate that Salmonella enterica serotype Typhi (S. Typhi) is a significant cause of morbidity and mortality in Africa. With limited anticipated short-term improvements in sanitation and water infrastructure, targeted vaccination campaigns may be an important prevention tool for typhoid fever. A cross-sectional survey was conducted with 435 randomly selected households in four rural villages on Pemba Island, Tanzania. A dichotomous 'readiness to pay' variable was created to assess vaccine desirability. Data analyses included univariate and bivariate descriptive statistics and binary logistic regression. Bivariate outcomes (ANOVA, t-tests, and chi-square) and odds ratios with 95% confidence intervals are reported. A total of 66% respondents stated that they would pay for a typhoid fever vaccine in the future. Readiness to pay was not significantly associated with household expenditures. Readiness to pay was associated with use of local Primary Health Care Units (PHCUs) compared to use of cottage or district hospitals (OR 1.8 [95% CI, 1.2-2.7]: p=.007) and with knowledge of someone being sick from typhoid fever (OR 2.2 [95% CI, 1.0-4.5]: p=.039). Respondents perceiving prevention measures as more effective (OR 1.0 [95% CI, 1.0-1.2]: p=.009) were also more likely ready to pay. Preferred methods of communication of information about a typhoid fever vaccine included broadcasting via microphone ('miking'), radio, and door-to-door visits. With rapid increase in numbers of licensed and promising vaccines, policy makers and health administrators are faced with decisions regarding allocation of scarce health resources for competing interventions. Community residents need to be informed about diseases which may not be readily recognized, diagnosed, and treated. Perceived vulnerability to the disease may increase likelihood of vaccine desirability. A better local understanding of typhoid fever is needed for general prevention measures, increasing treatment access, and future vaccination campaigns. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biofilm Formation Protects Salmonella from the Antibiotic Ciprofloxacin In Vitro and In Vivo in the Mouse Model of chronic Carriage.

PubMed

González, Juan F; Alberts, Halley; Lee, Joel; Doolittle, Lauren; Gunn, John S

2018-01-09

Typhoid fever is caused by the human-restricted pathogen Salmonella enterica sv. Typhi. Approximately 5% of people that resolve the disease become chronic carriers, with the gallbladder as the main reservoir of the bacteria. Of these, about 90% present with gallstones, on which Salmonella form biofilms. Because S. Typhi is a human-restricted pathogen, these carriers are the main source of dissemination of the disease; unfortunately, antibiotic treatment has shown to be an ineffective therapy. This is believed to be caused by the inherent antibiotic resistance conferred by Salmonella biofilms growing on gallstones. The gallstone mouse model with S. Typhimurium has proven to be an excellent surrogate for S. Typhi chronic infection. In this study, we test the hypothesis that the biofilm state confers Salmonella with the increased resistance to antibiotics observed in cases of chronic carriage. We found that, in the biofilm state, Salmonella is significantly more resistant to ciprofloxacin, a common antibiotic used for the treatment of Salmonella, both in vitro (p < 0.001 for both S. Typhi and S. Typhimurium with respect to planktonic cells) and in vivo (p = 0.0035 with respect to control mice).

Development of an acid-resistant Salmonella Typhi Ty21a attenuated vector for improved oral vaccine delivery

USDA-ARS?s Scientific Manuscript database

The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, T...

Lactose-fermenting, multiple drug-resistant Salmonella typhi strains isolated from a patient with postoperative typhoid fever.

PubMed Central

Kohbata, S; Takahashi, M; Yabuuchi, E

1983-01-01

Two lactose-fermenting Salmonella typhi strains were isolated from bile and blood specimens of a typhoid fever patient who underwent a cholecystectomy due to cholelithiasis. One lactose-fermenting S. typhi strain was also isolated from a pus specimen which was obtained at the tip of the T-shaped tube withdrawn from the operative wound of the common bile duct of the patient. These three lactose-fermenting isolates: GIFU 11924 from bile, GIFU 11926 from pus, and GIFU 11927 from blood, were phenotypically identical to the type strain (GIFU 11801 = ATCC 19430 = NCTC 8385) of S. typhi, except that the three strains fermented lactose and failed to blacken the butt of Kligler iron agar or triple sugar iron agar medium. All three lactose-fermenting strains were resistant to chloramphenicol, ampicillin, sulfomethoxazole, trimethoprim, gentamicin, cephaloridine, and four other antimicrobial agents. The type strain was uniformly susceptible to these 10 drugs. The strain GIFU 11925, a lactose-negative dissociant from strain GIFU 11926, was also susceptible to these drugs, with the sole exception of chloramphenicol (minimal inhibitory concentration, 100 micrograms/ml). PMID:6630471

Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis.

PubMed

Non, Lemuel R; Patel, Rupa; Esmaeeli, Amir; Despotovic, Vladimir

2015-11-01

Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid fever from Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from India who presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis. © The American Society of Tropical Medicine and Hygiene.

Identification of carriers among individuals recruited in the typhoid registry in Malaysia using stool culture, polymerase chain reaction, and dot enzyme immunoassay as detection tools.

PubMed

Chua, Ang Lim; Aziah, Ismail; Balaram, Prabha; Bhuvanendran, Saatheeyavaane; Anthony, Amy Amilda; Mohmad, Siti Norazura; Nasir, Norhafiza M; Hassan, Haslizai; Naim, Rochman; Meran, Lila P; Hussin, Hani M; Ismail, Asma

2015-03-01

Chronic carriers of Salmonella Typhi act as reservoirs for the organism and become the agents of typhoid outbreaks in a community. In this study, chronic carriers in Kelantan, Malaysia were first identified using the culture and polymerase chain reaction method. Then, a novel serological tool, designated Typhidot-C, was evaluated in retrospect using the detected individuals as control positives. Chronic carriage positive by the culture and polymerase chain reaction method was recorded at 3.6% (4 out of 110) among individuals who previously had acute typhoid fever and a 9.4% (10 out of 106) carriage rate was observed among food handlers screened during outbreaks. The Typhidot-C assay was able to detect all these positive carriers showing its potential as a viable carrier screening tool and can be used for efficient detection of typhoid carriers in an endemic area. These findings were used to establish the first carrier registry for S Typhi carriers in Malaysia. © 2012 APJPH.

Enteric Fever in a Tertiary Paediatric Hospital: A Retrospective Six-Year Review.

PubMed

Ahmad Hatib, Nur Adila; Chong, Chia Yin; Thoon, Koh Cheng; Tee, Nancy Ws; Krishnamoorthy, Subramania S; Tan, Natalie Wh

2016-07-01

Enteric fever is a multisystemic infection which largely affects children. This study aimed to analyse the epidemiology, clinical presentation, treatment and outcome of paediatric enteric fever in Singapore. A retrospective review of children diagnosed with enteric fever in a tertiary paediatric hospital in Singapore was conducted from January 2006 to January 2012. Patients with positive blood cultures for Salmonella typhi or paratyphi were identified from the microbiology laboratory information system. Data was extracted from their case records. Of 50 enteric fever cases, 86% were due to Salmonella typhi, with 16.3% being multidrug resistant (MDR) strains. Sixty-two percent of S. typhi isolates were of decreased ciprofloxacin susceptibility (DCS). Five cases were both MDR and DCS. The remaining 14% were Salmonella paratyphi A. There were only 3 indigenous cases. Ninety-four percent had travelled to typhoid-endemic countries, 70.2% to the Indian subcontinent and the rest to Indonesia and Malaysia. All patients infected with MDR strains had travelled to the Indian subcontinent. Anaemia was a significant finding in children with typhoid, as compared to paratyphoid fever (P = 0.04). Although all children were previously well, 14% suffered severe complications including shock, pericardial effusion and enterocolitis. None had typhoid vaccination prior to their travel to developing countries. Enteric fever is largely an imported disease in Singapore and has contributed to significant morbidity in children. The use of typhoid vaccine, as well as education on food and water hygiene to children travelling to developing countries, needs to be emphasised.

Salmonella enterica Serotype Napoli is the First Cause of Invasive Nontyphoidal Salmonellosis in Lombardy, Italy (2010-2014), and Belongs to Typhi Subclade.

PubMed

Huedo, Pol; Gori, Maria; Zolin, Anna; Amato, Ettore; Ciceri, Giulia; Bossi, Anna; Pontello, Mirella

2017-03-01

Salmonella enterica serotype Napoli (S. Napoli) is currently emerging in Europe and particularly in Italy, where in 2014 it caused a large outbreak associated with elevated rates of bacteremia. However, no study has yet investigated its invasive ability and phylogenetic classification. Here, we show that between 2010 and 2014, S. Napoli was the first cause of invasive salmonellosis affecting 40 cases out of 687 (invasive index: 5.8%), which is significantly higher than the invasive index of all the other nontyphoidal serotypes (2.0%, p < 0.05). Genomic and phylogenetic analyses of an invasive isolate revealed that S. Napoli belongs to Typhi subclade in clade A, Paratyphi A being the most related serotype and carrying almost identical pattern of typhoid-associated genes. This work presents evidence of invasive capacity of S. Napoli and argues for reconsideration of its nontyphoidal category.

Risk factors for the development of severe typhoid fever in Vietnam.

PubMed

Parry, Christopher M; Thompson, Corinne; Vinh, Ha; Chinh, Nguyen Tran; Phuong, Le Thi; Ho, Vo Anh; Hien, Tran Tinh; Wain, John; Farrar, Jeremy J; Baker, Stephen

2014-02-10

Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever. We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993-1995 and 1997-1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission. The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00-2.57; p = 0.035). In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was independently associated with disease severity. During this period many patients were being treated with fluoroquinolones prior to hospital admission. Ciprofloxacin and ofloxacin should be used with caution in patients infected with S. Typhi that have intermediate susceptibility to ciprofloxacin.

Risk factors for the development of severe typhoid fever in Vietnam

PubMed Central

2014-01-01

Background Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever. Methods We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993–1995 and 1997–1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission. Results The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00-2.57; p = 0.035). Conclusions In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was independently associated with disease severity. During this period many patients were being treated with fluoroquinolones prior to hospital admission. Ciprofloxacin and ofloxacin should be used with caution in patients infected with S. Typhi that have intermediate susceptibility to ciprofloxacin. PMID:24512443

Functional selection of a type IV pili-binding peptide that specifically inhibits Salmonella Typhi adhesion to/invasion of human monocytic cells.

PubMed

Wu, Hong-Yan; Zhang, Xiao-Lian; Pan, Qin; Wu, Jianguo

2005-11-01

Salmonella enterica serovar Typhi (S. Typhi) is an important pathogen which infects humans exclusively and causes typhoid or enteric fever. Recently it has been discovered that type IVB pili, encoded by the S. Typhi pil operon located in the major pathogenicity island, may be important in the pathogenesis of epidemic enteric fever. To further investigate the roles of type IVB pili of S. Typhi, a 12-mer peptide (RQERSSLSKPVV), binding to the structural protein PilS of the type IVB pili of S. Typhi, was isolated with a ribosome display system. This peptide was designated as peptide R. We found that peptide R inhibited adhesion to/invasion of human monocytic THP-1 cells by piliated S. Typhi bacteria, but had no effects on nonpiliated S. Typhi bacteria. A random 12-mer peptide, of size and solubility equal to peptide R, served as a control on the specificity of peptide R. The specific interaction and binding equilibrium between the 12-mer peptide R and PilS protein was determined by isothermal titration calorimetry (ITC) and a binding constant Ka determined to be between 0.4 x 10(5) and 2.2 x 10(5)L mol(-1). Our findings suggest that the type IV pili-binding peptide R holds potential as an antibacterial peptide effective against S. Typhi infections, both in terms of prevention and therapeutic treatment. The data further provide insights into the understanding of the pathogenic roles of the type IVB pili of S. Typhi.

Restaurant-associated outbreak of typhoid fever in Maryland: identification of carrier facilitated by measurement of serum Vi antibodies.

PubMed Central

Lin, F Y; Becke, J M; Groves, C; Lim, B P; Israel, E; Becker, E F; Helfrich, R M; Swetter, D S; Cramton, T; Robbins, J B

1988-01-01

Ten cases of typhoid fever occurred between 24 August and 1 September 1986 in the vicinity of Silver Spring, Md. Shrimp salad served in a fast-food restaurant was implicated as the source of infection. Stool cultures were obtained from 104 employees, and serum Vi antibodies were assayed in 97 of the employees. Salmonella typhi was isolated from stool cultures of an 18-year-old asymptomatic female employee, who was a food handler. A high level of Vi antibodies (79.0 micrograms/ml), measured by radioimmunoassay, was found in her serum. She had emigrated from an endemic area at the age of 14 years and had visited that endemic area 2 years previously. The causal relation between the carrier and the 10 cases of typhoid fever was confirmed by a common bacteriophage type, denoted "degraded Vi resembling O," in the S. typhi isolates. This phage type is rare in the western hemisphere but common in the endemic area from which the carrier had emigrated. The high level of Vi antibody in the asymptomatic carrier, in contrast to the lower levels in the convalescent- and postimmunization-phase sera, facilitated the identification of the source infection in this outbreak. This radioimmunoassay offers a rapid and standardized method for identifying carriers of S. typhi. PMID:3384930

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

PubMed Central

Sabbagh, Sébastien C.; Lepage, Christine; McClelland, Michael; Daigle, France

2012-01-01

The human-adapted Salmonella enterica serovar Typhi (S. Typhi) causes a systemic infection known as typhoid fever. This disease relies on the ability of the bacterium to survive within macrophages. In order to identify genes involved during interaction with macrophages, a pool of approximately 105 transposon mutants of S. Typhi was subjected to three serial passages of 24 hours through human macrophages. Mutants recovered from infected macrophages (output) were compared to the initial pool (input) and those significantly underrepresented resulted in the identification of 130 genes encoding for cell membrane components, fimbriae, flagella, regulatory processes, pathogenesis, and many genes of unknown function. Defined deletions in 28 genes or gene clusters were created and mutants were evaluated in competitive and individual infection assays for uptake and intracellular survival during interaction with human macrophages. Overall, 26 mutants had defects in the competitive assay and 14 mutants had defects in the individual assay. Twelve mutants had defects in both assays, including acrA, exbDB, flhCD, fliC, gppA, mlc, pgtE, typA, waaQGP, SPI-4, STY1867-68, and STY2346. The complementation of several mutants by expression of plasmid-borne wild-type genes or gene clusters reversed defects, confirming that the phenotypic impairments within macrophages were gene-specific. In this study, 35 novel phenotypes of either uptake or intracellular survival in macrophages were associated with Salmonella genes. Moreover, these results reveal several genes encoding molecular mechanisms not previously known to be involved in systemic infection by human-adapted typhoidal Salmonella that will need to be elucidated. PMID:22574205

Differential roles for pathogenicity islands SPI-13 and SPI-8 in the interaction of Salmonella Enteritidis and Salmonella Typhi with murine and human macrophages.

PubMed

Espinoza, Rodrigo A; Silva-Valenzuela, Cecilia A; Amaya, Fernando A; Urrutia, Ítalo M; Contreras, Inés; Santiviago, Carlos A

2017-02-15

Salmonella pathogenicity island (SPI)-13 is conserved in many serovars of S. enterica, including S. Enteritidis, S. Typhimurium and S. Gallinarum. However, it is absent in typhoid serovars such as S. Typhi and Paratyphi A, which carry SPI-8 at the same genomic location. Because the interaction with macrophages is a critical step in Salmonella pathogenicity, in this study we investigated the role played by SPI-13 and SPI-8 in the interaction of S. Enteritidis and S. Typhi with cultured murine (RAW264.7) and human (THP-1) macrophages. Our results showed that SPI-13 was required for internalization of S. Enteritidis in murine but not human macrophages. On the other hand, SPI-8 was not required for the interaction of S. Typhi with human or murine macrophages. Of note, the presence of an intact copy of SPI-13 in a S. Typhi mutant carrying a deletion of SPI-8 did not improve its ability to be internalized by, or survive in human or murine macrophages. Altogether, our results point out to different roles for SPI-13 and SPI-8 during Salmonella infection. While SPI-13 contributes to the interaction of S. Enteritidis with murine macrophages, SPI-8 is not required in the interaction of S. Typhi with murine or human macrophages. We hypothesized that typhoid serovars have lost SPI-13 and maintained SPI-8 to improve their fitness during another phase of human infection.

Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa.

PubMed

Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen

2017-05-09

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

Antagonistic Activity of Lactobacillus Isolates against Salmonella typhi In Vitro

PubMed Central

Abdel-Daim, Amira; Hassouna, Nadia; Hafez, Mohamed; Ashor, Mohamed Seif Aldeen; Aboulwafa, Mohammad M.

2013-01-01

Background. Enteric fever is a global health problem, and rapidly developing resistance to various drugs makes the situation more alarming. The potential use of Lactobacillus to control typhoid fever represents a promising approach, as it may exert protective actions through various mechanisms. Methods. In this study, the probiotic potential and antagonistic activities of 32 Lactobacillus isolates against Salmonella typhi were evaluated. The antimicrobial activity of cell free supernatants of Lactobacillus isolates, interference of Lactobacillus isolates with the Salmonella adherence and invasion, cytoprotective effect of Lactobacillus isolates, and possibility of concurrent use of tested Lactobacillus isolates and antibiotics were evaluated by testing their susceptibilities to antimicrobial agents, and their oxygen tolerance was also examined. Results. The results revealed that twelve Lactobacillus isolates could protect against Salmonella typhi infection through interference with both its growth and its virulence properties, such as adherence, invasion, and cytotoxicity. These Lactobacillus isolates exhibited MIC values for ciprofloxacin higher than those of Salmonella typhi and oxygen tolerance and were identified as Lactobacillus plantarum. Conclusion. The tested Lactobacillus plantarum isolates can be introduced as potential novel candidates that have to be subjected for in vivo and application studies for treatment and control of typhoid fever. PMID:24191248

Endemic, Epidemic Clone of Salmonella enterica Serovar Typhi Harboring a Single Multidrug-Resistant Plasmid in Vietnam between 1995 and 2002

PubMed Central

Le, Thi Anh Hong; Lejay-Collin, Monique; Grimont, Patrick A. D.; Hoang, Thuy Long; Nguyen, Thi Vinh; Grimont, Francine; Scavizzi, Maurice R.

2004-01-01

Salmonella enterica serovar Typhi strains resistant to ampicillin, chloramphenicol, tetracyclines, streptomycin, and cotrimoxazole, isolated from sporadic cases and minor outbreaks in Vietnam between 1995 and 2002, were typed and compared. Plasmid fingerprinting, Vi bacteriophage typing, XbaI pulsed-field gel electrophoresis, and PstI ribotyping showed that endemic, epidemic multidrug-resistant typhoid fever was due, for at least 74.1% of the isolates, to one or two clones of serovar Typhi harboring a single resistance plasmid. PstI ribotyping was used as a basic technique to ensure that a serovar Typhi expansion was clonal. PMID:15243066

Vi-CRM 197 as a new conjugate vaccine against Salmonella Typhi.

PubMed

Micoli, F; Rondini, S; Pisoni, I; Proietti, D; Berti, F; Costantino, P; Rappuoli, R; Szu, S; Saul, A; Martin, L B

2011-01-17

An efficacious, low cost vaccine against typhoid fever, especially for young children, would make a major impact on disease burden in developing countries. The virulence capsular polysaccharide of Salmonella Typhi (Vi) coupled to recombinant mutant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) has been shown to be highly efficacious. We investigated the use of carrier proteins included in infant vaccines, standardized the conjugation process and developed key assays required for routine lot release at production scale. Vi from a BSL1 organism, Citrobacter freundii, strain WR7011, was used as an alternative to Vi from S. Typhi. We showed that Vi conjugated to CRM(197), a non-toxic mutant of diphtheria toxin, widely used in commercial vaccines, was produced at high yield. Vi-CRM(197) proved immunogenic in animal studies, even without adjuvant. Thus, Vi-CRM(197) appears to be a suitable candidate for the development of a commercially viable, effective typhoid vaccine for developing countries. Copyright © 2010 Elsevier Ltd. All rights reserved.

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

PubMed

Wong, Vanessa K; Baker, Stephen; Pickard, Derek J; Parkhill, Julian; Page, Andrew J; Feasey, Nicholas A; Kingsley, Robert A; Thomson, Nicholas R; Keane, Jacqueline A; Weill, François-Xavier; Edwards, David J; Hawkey, Jane; Harris, Simon R; Mather, Alison E; Cain, Amy K; Hadfield, James; Hart, Peter J; Thieu, Nga Tran Vu; Klemm, Elizabeth J; Glinos, Dafni A; Breiman, Robert F; Watson, Conall H; Kariuki, Samuel; Gordon, Melita A; Heyderman, Robert S; Okoro, Chinyere; Jacobs, Jan; Lunguya, Octavie; Edmunds, W John; Msefula, Chisomo; Chabalgoity, Jose A; Kama, Mike; Jenkins, Kylie; Dutta, Shanta; Marks, Florian; Campos, Josefina; Thompson, Corinne; Obaro, Stephen; MacLennan, Calman A; Dolecek, Christiane; Keddy, Karen H; Smith, Anthony M; Parry, Christopher M; Karkey, Abhilasha; Mulholland, E Kim; Campbell, James I; Dongol, Sabina; Basnyat, Buddha; Dufour, Muriel; Bandaranayake, Don; Naseri, Take Toleafoa; Singh, Shalini Pravin; Hatta, Mochammad; Newton, Paul; Onsare, Robert S; Isaia, Lupeoletalalei; Dance, David; Davong, Viengmon; Thwaites, Guy; Wijedoru, Lalith; Crump, John A; De Pinna, Elizabeth; Nair, Satheesh; Nilles, Eric J; Thanh, Duy Pham; Turner, Paul; Soeng, Sona; Valcanis, Mary; Powling, Joan; Dimovski, Karolina; Hogg, Geoff; Farrar, Jeremy; Holt, Kathryn E; Dougan, Gordon

2015-06-01

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events

PubMed Central

Wong, Vanessa K; Baker, Stephen; Pickard, Derek J; Parkhill, Julian; Page, Andrew J; Feasey, Nicholas A; Kingsley, Robert A; Thomson, Nicholas R; Keane, Jacqueline A; Weill, François-Xavier; Edwards, David J; Hawkey, Jane; Harris, Simon R; Mather, Alison E; Cain, Amy K; Hadfield, James; Hart, Peter J; Thieu, Nga Tran Vu; Klemm, Elizabeth J; Glinos, Dafni A; Breiman, Robert F; Watson, Conall H; Kariuki, Samuel; Gordon, Melita A; Heyderman, Robert S; Okoro, Chinyere; Jacobs, Jan; Lunguya, Octavie; Edmunds, W John; Msefula, Chisomo; Chabalgoity, Jose A; Kama, Mike; Jenkins, Kylie; Dutta, Shanta; Marks, Florian; Campos, Josefina; Thompson, Corinne; Obaro, Stephen; MacLennan, Calman A; Dolecek, Christiane; Keddy, Karen H; Smith, Anthony M; Parry, Christopher M; Karkey, Abhilasha; Mulholland, E Kim; Campbell, James I; Dongol, Sabina; Basnyat, Buddha; Dufour, Muriel; Bandaranayake, Don; Naseri, Take Toleafoa; Singh, Shalini Pravin; Hatta, Mochammad; Newton, Paul; Onsare, Robert S; Isaia, Lupeoletalalei; Dance, David; Davong, Viengmon; Thwaites, Guy; Wijedoru, Lalith; Crump, John A; De Pinna, Elizabeth; Nair, Satheesh; Nilles, Eric J; Thanh, Duy Pham; Turner, Paul; Soeng, Sona; Valcanis, Mary; Powling, Joan; Dimovski, Karolina; Hogg, Geoff; Farrar, Jeremy; Holt, Kathryn E; Dougan, Gordon

2016-01-01

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species. PMID:25961941

Functional Analysis of the Chaperone-Usher Fimbrial Gene Clusters of Salmonella enterica serovar Typhi.

PubMed

Dufresne, Karine; Saulnier-Bellemare, Julie; Daigle, France

2018-01-01

The human-specific pathogen Salmonella enterica serovar Typhi causes typhoid, a major public health issue in developing countries. Several aspects of its pathogenesis are still poorly understood. S . Typhi possesses 14 fimbrial gene clusters including 12 chaperone-usher fimbriae ( stg, sth, bcf , fim, saf , sef , sta, stb, stc, std, ste , and tcf ). These fimbriae are weakly expressed in laboratory conditions and only a few are actually characterized. In this study, expression of all S . Typhi chaperone-usher fimbriae and their potential roles in pathogenesis such as interaction with host cells, motility, or biofilm formation were assessed. All S . Typhi fimbriae were better expressed in minimal broth. Each system was overexpressed and only the fimbrial gene clusters without pseudogenes demonstrated a putative major subunits of about 17 kDa on SDS-PAGE. Six of these (Fim, Saf, Sta, Stb, Std, and Tcf) also show extracellular structure by electron microscopy. The impact of fimbrial deletion in a wild-type strain or addition of each individual fimbrial system to an S . Typhi afimbrial strain were tested for interactions with host cells, biofilm formation and motility. Several fimbriae modified bacterial interactions with human cells (THP-1 and INT-407) and biofilm formation. However, only Fim fimbriae had a deleterious effect on motility when overexpressed. Overall, chaperone-usher fimbriae seem to be an important part of the balance between the different steps (motility, adhesion, host invasion and persistence) of S . Typhi pathogenesis.

Neurologic manifestations associated with an outbreak of typhoid fever, Malawi--Mozambique, 2009: an epidemiologic investigation.

PubMed

Sejvar, James; Lutterloh, Emily; Naiene, Jeremias; Likaka, Andrew; Manda, Robert; Nygren, Benjamin; Monroe, Stephan; Khaila, Tadala; Lowther, Sara A; Capewell, Linda; Date, Kashmira; Townes, David; Redwood, Yanique; Schier, Joshua; Barr, Beth Tippett; Demby, Austin; Mallewa, Macpherson; Kampondeni, Sam; Blount, Ben; Humphrys, Michael; Talkington, Deborah; Armstrong, Gregory L; Mintz, Eric

2012-01-01

The bacterium Salmonella enterica serovar Typhi causes typhoid fever, which is typically associated with fever and abdominal pain. An outbreak of typhoid fever in Malawi-Mozambique in 2009 was notable for a high proportion of neurologic illness. Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique Persons meeting a clinical case definition were identified through surveillance, with laboratory confirmation of typhoid by antibody testing or blood/stool culture. We gathered demographic and clinical information, examined patients, and evaluated a subset of patients 11 months after onset. A sample of persons with and without neurologic signs was tested for vitamin B6 and B12 levels and urinary thiocyanate. Between March - November 2009, 303 cases of typhoid fever were identified. Forty (13%) persons had objective neurologic findings, including 14 confirmed by culture/serology; 27 (68%) were hospitalized, and 5 (13%) died. Seventeen (43%) had a constellation of upper motor neuron findings, including hyperreflexia, spasticity, or sustained ankle clonus. Other neurologic features included ataxia (22, 55%), parkinsonism (8, 20%), and tremors (4, 10%). Brain MRI of 3 (ages 5, 7, and 18 years) demonstrated cerebral atrophy but no other abnormalities. Of 13 patients re-evaluated 11 months later, 11 recovered completely, and 2 had persistent hyperreflexia and ataxia. Vitamin B6 levels were markedly low in typhoid fever patients both with and without neurologic signs. Neurologic signs may complicate typhoid fever, and the diagnosis should be considered in persons with acute febrile neurologic illness in endemic areas.

Epidemiology, clinical presentation, and patterns of drug resistance of Salmonella Typhi in Karachi, Pakistan.

PubMed

Khan, M Imran; Soofi, Sajid Bashir; Ochiai, R Leon; Khan, Mohammad Jawed; Sahito, Shah Muhammad; Habib, Mohammad Atif; Puri, Mahesh K; Von Seidlein, Lorenz; Park, Jin Kyung; You, Young Ae; Ali, Mohammad; Nizami, S Qamarudding; Acosta, Camilo J; Sack, R Bradley; Clemens, John D; Bhutta, Zulfiqar A

2012-10-19

Enteric fever remains a major public health problem in Asia. Planning appropriate preventive measures such as immunization requires a clear understanding of disease burden. We conducted a community-based surveillance for Salmonella Typhi infection in children in Karachi, Pakistan. A de jure household census was conducted at baseline in the study setting to enumerate all individuals. A health-care facility-based passive surveillance system was used to capture episodes of fever lasting three or more 3 days in children 2 to 16 years old. A total of 7,401 blood samples were collected for microbiological confirmation, out of which 189 S. Typhi and 32 S. Paratyphi A isolates were identified with estimated annual incidences of 451/100,000 (95% CI: 446 - 457) and 76/100,000 (95% CI: 74 - 78) respectively. At the time of presentation, after adjusting for age, there was an association between the duration of fever and temperature at presentation, and being infected with multidrug-resistant S. Typhi. Of 189 isolates 83 were found to be resistant to first-line antimicrobial therapy. There was no statistically significant difference in clinical presentation of blood culture sensitive and resistant S. Typhi isolates. Incidence of S. Typhi in children is high in urban squatter settlements of Karachi, Pakistan. Findings from this study identified duration of fever and temperature at the time of presentation as important symptoms associated with blood culture-confirmed typhoid fever. Preventive strategies such as immunization and improvements in water and sanitation conditions should be the focus of typhoid control in urban settlements of Pakistan.

Evaluation of Salmonella enterica serovar Typhi (Ty2 aroC-ssaV-) M01ZH09, with a defined mutation in the Salmonella pathogenicity island 2, as a live, oral typhoid vaccine in human volunteers.

PubMed

Kirkpatrick, B D; McKenzie, Robin; O'Neill, J Patrick; Larsson, Catherine J; Bourgeois, A Louis; Shimko, Janet; Bentley, Matthew; Makin, Jill; Chatfield, Steve; Hindle, Zoë; Fidler, Christine; Robinson, Brad E; Ventrone, Cassandra H; Bansal, Nivedita; Carpenter, Colleen M; Kutzko, Deborah; Hamlet, Sandra; LaPointe, Casey; Taylor, David N

2006-01-12

Salmonella enterica serovar Typhi strains with mutations in the Salmonella pathogenicity island-2 (SPI-2) may represent an effective strategy for human vaccine development, and a vectoring system for heterologous antigens. S. Typhi (Ty2 aroC-ssaV-) M01ZH09 is an attenuated, live, oral typhoid vaccine harboring defined deletion mutations in ssaV, which encodes an integral component in the SPI-2 type III secretion system (TTSS), as well as a mutation in an aromatic biosynthetic pathway needed for bacterial growth in vivo (aroC). SPI-2 mutant vaccines have yet to be evaluated in a large, randomized human trial. A simplified or single-oral dose oral typhoid vaccine using the SPI-2 strategy would offer significant advantages over the currently licensed typhoid vaccines. We performed a double-blinded, placebo-controlled, dose-escalating clinical trial in 60 healthy adult volunteers to determine the tolerability and immunogenicity of a single dose of M01ZH09. Three groups of 20 healthy adult volunteers were enrolled; 16 in each group received a single oral dose of the freeze-dried vaccine at 5 x 10(7), 5 x 10(8) or 5 x 10(9)CFU in a bicarbonate buffer. Four volunteers in each cohort received placebo in the same buffer. Adverse events were infrequent and not statistically different between vaccine and placebo recipients, although two subjects in the mid-range dose and three subjects in the highest dose had temperature measurements >37.5 degrees C. No blood or urine cultures were positive for M01ZH09, and fecal shedding was brief. The immune response was dose-related; the highest vaccine dose (5 x 10(9)CFU) was the most immunogenic. All tested subjects receiving the highest dose had a significant ASC response (mean 118 spots/10(6) cells). A >or=4-fold increase in antibody titer for S. Typhi LPS or flagellin was detected in 75% of volunteers in the highest-dose cohort by day 28. The SPI-2 mutant vaccine, M01ZH09, is a promising typhoid vaccine candidate and deserves further study as a vectoring system for heterologous vaccine antigens.

First report on antimicrobial resistance and molecular characterization of Salmonella enterica serotype Typhi isolated from human specimens in Luanda, Angola.

PubMed

Francisco, Moisés; Costa, Sofia Santos; Belas, Adriana; Ramos, Jorge; Couto, Isabel; Pomba, Constança; Viveiros, Miguel

2018-02-09

Typhoid fever is a common infection in Africa and in spite of scarce surveillance reports, its incidence is commonly considered high by the Angolan Health system. Drug-resistant Salmonella enterica serotype Typhi has emerged, turning antimicrobial susceptibility testing essential to provide clinical guidance. This is the first report analyzing antimicrobial resistance patterns and population structure of the few S. enterica ser. Typhi isolated from patients with Typhoid fever in Luanda, Angola. Isolates were collected by the National Institute of Public Health of Angola, between September 2013 and May 2014. A total of 10 isolates were identified by API20E system and serotyping, and the genus confirmed by PCR. All isolates were tested for antibiotic susceptibility and the presence of resistance genes (blaCTX-M, blaSHV, blaTEM, blaOXA-1, several plasmid-borne genes encoding AmpC β-lactamases, sul and qnr genes, dfrIa, dfrA12, aac(6')- Ib, cmlA and floR) screened by PCR. Isolates were typed by PFGE and MLST. Several isolates were identified with resistance to trimethoprim-sulfamethoxazole (n=6), beta-lactams (n=5), chloramphenicol (n=1) and reduced susceptibility to ciprofloxacin (n=2). PFGE revealed eight closely related restriction patterns and MLST grouped these in three sequence types: ST1, ST2 and ST8, with ST2 being predominant. This first epidemiological report provides a preliminary portray of the S. enterica ser. Typhi strains that circulate in Luanda, Angola and emphasizes the demand for a continuous monitoring of this pathogen to provide information to implement better epidemiological strategies for the control of Typhoid fever in Angola. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa

PubMed Central

Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen

2017-01-01

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics. DOI: http://dx.doi.org/10.7554/eLife.15651.001 PMID:28483042

Mathematical Modeling to Assess the Drivers of the Recent Emergence of Typhoid Fever in Blantyre, Malawi.

PubMed

Pitzer, Virginia E; Feasey, Nicholas A; Msefula, Chisomo; Mallewa, Jane; Kennedy, Neil; Dube, Queen; Denis, Brigitte; Gordon, Melita A; Heyderman, Robert S

2015-11-01

Multiyear epidemics of Salmonella enterica serovar Typhi have been reported from countries across eastern and southern Africa in recent years. In Blantyre, Malawi, a dramatic increase in typhoid fever cases has recently occurred, and may be linked to the emergence of the H58 haplotype. Strains belonging to the H58 haplotype often exhibit multidrug resistance and may have a fitness advantage relative to other Salmonella Typhi strains. To explore hypotheses for the increased number of typhoid fever cases in Blantyre, we fit a mathematical model to culture-confirmed cases of Salmonella enterica infections at Queen Elizabeth Central Hospital, Blantyre. We explored 4 hypotheses: (1) an increase in the basic reproductive number (R0) in response to increasing population density; (2) a decrease in the incidence of cross-immunizing infection with Salmonella Enteritidis; (3) an increase in the duration of infectiousness due to failure to respond to first-line antibiotics; and (4) an increase in the transmission rate following the emergence of the H58 haplotype. Increasing population density or decreasing cross-immunity could not fully explain the observed pattern of typhoid emergence in Blantyre, whereas models allowing for an increase in the duration of infectiousness and/or the transmission rate of typhoid following the emergence of the H58 haplotype provided a good fit to the data. Our results suggest that an increase in the transmissibility of typhoid due to the emergence of drug resistance associated with the H58 haplotype may help to explain recent outbreaks of typhoid in Malawi and similar settings in Africa. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Antibacterial effect of mango (Mangifera indica Linn.) leaf extract against antibiotic sensitive and multi-drug resistant Salmonella typhi.

PubMed

Hannan, Abdul; Asghar, Samra; Naeem, Tahir; Ikram Ullah, Muhammad; Ahmed, Ijaz; Aneela, Syeda; Hussain, Shabbir

2013-07-01

Alternative herbal medicine has been used to treat various infections from centuries. Natural plants contain phytoconstituents having similar chemical properties as of synthetic antibiotics. Typhoid fever is a serious infection and failure of its treatment emerged multi-drug resistant (MDR) bugs of Salmonella typhi. Due to multiple and repeated issues with antibiotics efficacy, it became essential to evaluate biological properties of plants from different geographical origins. Mango leaves have been Reported for various medicinal effects like antioxidant, antimicrobial, antihelminthic, antidiabetic and antiallergic etc. Objective of present study was to investigate anti-typhoid properties of acetone mango leaf extract (AMLE) against antibiotic sensitive and MDR S. typhi isolates. A total of 50 isolates of S. typhi including MDR (n=30) and antibiotic sensitive (n=20) were investigated. Staphylococcus aureus (ATCC 25923) and Salmonella typhimurium (ATCC14028) were used as quality control strains. AMLE was prepared and its antibacterial activity was evaluated by agar well diffusion screening method and minimum inhibitory concentration (MIC), by agar dilution technique. Zone of inhibition (mm) of AMLE against MDR and antibiotic sensitive isolates was 18±1.5mm (Mean±S.D). Zone of S. aureus (ATCC 25923) and S. typhimurium (ATCC14028) was 20±1.5mm (Mean±S.D). MIC of AMLE was Reported in range from 10-50 mg/ml. The present study described the inhibitory effects of mango leaves against S. typhi.

First characterization of immunogenic conjugates of Vi negative Salmonella Typhi O-specific polysaccharides with rEPA protein for vaccine development.

PubMed

Salman, M; St Michael, F; Ali, A; Jabbar, A; Cairns, C; Hayes, A C; Rahman, M; Iqbal, M; Haque, A; Cox, A D

2017-11-01

Efficacious typhoid vaccines for young children will significantly reduce the disease burden in developing world. The Vi polysaccharide based conjugate vaccines (Vi-rEPA) against Salmonella Typhi Vi positive strains has shown high efficacy but may be ineffective against Vi negative S. Typhi. In this study, for the first time, we report the synthesis and evaluation of polysaccharide-protein conjugates of Vi negative S. Typhi as potential vaccine candidates. Four different conjugates were synthesized using recombinant exoprotein A of Pseudomonas aeruginosa (rEPA) and human serum albumin (HSA) as the carrier proteins, using either direct reductive amination or an intermediate linker molecule, adipic acid dihydrazide (ADH). Upon injection into mice, a significantly higher antibody titer was observed in mice administrated with conjugate-1 (OSP-HSA) (P=0.0001) and conjugate 2 (OSP-rEPA) (P≤0.0001) as compared to OSP alone. In contrast, the antibody titer elicited by conjugate 3 (OSP ADH -HSA) and conjugate 4 (OSP ADH -rEPA) were insignificant (P=0.1684 and P=0.3794, respectively). We conclude that reductive amination is the superior method to prepare the S. Typhi OSP glycoconjugate. Moreover, rEPA was a better carrier protein than HSA. Thus OSP-rEPA conjugate seems to be efficacious typhoid vaccines candidate, it may be evaluated further and recommended for the clinical trials. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Structural Basis of Typhoid: Salmonella typhi Type IVb pilin (PilS) and Cystic Fibrosis Transmembrane Conductance Regulatory Interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balakrishna, A.; Saxena, A; Mok, H

2009-01-01

The type IVb pilus of the enteropathogenic bacteria Salmonella typhi is a major adhesion factor during the entry of this pathogen into gastrointestinal epithelial cells. Its target of adhesion is a stretch of 10 residues from the first extracellular domain of cystic fibrosis transmembrane conductance regulator (CFTR). The crystal structure of the N-terminal 25 amino acid deleted S. typhi native PilS protein (PilS), which makes the pilus, was determined at 1.9 A resolution by the multiwavelength anomalous dispersion method. Also, the structure of the complex of PilS and a target CFTR peptide, determined at 1.8 A, confirms that residues 113-117more » (NKEER) of CFTR are involved in binding with the pilin protein and gives us insight on the amino acids that are essential for binding. Furthermore, we have also explored the role of a conserved disulfide bridge in pilus formation. The subunit structure and assembly architecture are crucial for understanding pilus functions and designing suitable therapeutics against typhoid.« less

A multiplex single nucleotide polymorphism typing assay for detecting mutations that result in decreased fluoroquinolone susceptibility in Salmonella enterica serovars Typhi and Paratyphi A

PubMed Central

Song, Yajun; Roumagnac, Philippe; Weill, François-Xavier; Wain, John; Dolecek, Christiane; Mazzoni, Camila J.; Holt, Kathryn E.; Achtman, Mark

2010-01-01

Objectives Decreased susceptibility to fluoroquinolones has become a major problem for the successful therapy of human infections caused by Salmonella enterica, especially the life-threatening typhoid and paratyphoid fevers. Methods By using Luminex xTAG beads, we developed a rapid, reliable and cost-effective multiplexed genotyping assay for simultaneously detecting 11 mutations in gyrA, gyrB and parE of S. enterica serovars Typhi and Paratyphi A that result in nalidixic acid resistance (NalR) and/or decreased susceptibility to fluoroquinolones. Results This assay yielded unambiguous single nucleotide polymorphism calls on extracted DNA from 292 isolates of Salmonella Typhi (NalR = 223 and NalS = 69) and 106 isolates of Salmonella Paratyphi A (NalR = 24 and NalS = 82). All of the 247 NalR Salmonella Typhi and Salmonella Paratyphi A isolates were found to harbour at least one of the target mutations, with GyrA Phe-83 as the most common one (143/223 for Salmonella Typhi and 18/24 for Salmonella Paratyphi A). We also identified three GyrB mutations in eight NalS Salmonella Typhi isolates (six for GyrB Phe-464, one for GyrB Leu-465 and one for GyrB Asp-466), and mutations GyrB Phe-464 and GyrB Asp-466 seem to be related to the decreased ciprofloxacin susceptibility phenotype in Salmonella Typhi. This assay can also be used directly on boiled single colonies. Conclusions The assay presented here would be useful for clinical and reference laboratories to rapidly screen quinolone-resistant isolates of Salmonella Typhi and Salmonella Paratyphi A, and decipher the underlying genetic changes for epidemiological purposes. PMID:20511368

Gallbladder perforation complicating typhoid fever: report of two cases.

PubMed

Gali, B M; Ali, N; Agbese, G O; Duna, V D; Dawha, S D; Ismai, G I; Mohammed, M

2011-01-01

Gallbladder perforation (GBP) is rare and as a complication of typhoid fever is extremely rare. We present two consecutive patients with GBP diagnosed incidentally at laparotomy. Information on the management of two patients with gallbladder perforation seen at Federal Medical Centre Azare in June and October 2008 was extracted from their case records. The two patients were both males aged 13 years and 16 years. They both presented with high fever of more than 2 weeks duration; and abdominal pain and distension. Both patients had features of generalised peritonitis. Pre-operative diagnoses of typhoid enteric perforation were made based on a positive Widal test. Intra-operative findings however, were that of bile peritonitis and gallbladder perforation. Both had cholecystectomy. Culture of the bile aspirate yielded Salmonella typhi. Gallbladder perforation secondary to typhoid fever should be considered as a differential diagnosis in patients with suspected typhoid enteric perforation in typhoid fever endemic region.

A comparative study of Widal test with blood culture in the diagnosis of typhoid fever in febrile patients.

PubMed

Andualem, Gizachew; Abebe, Tamrat; Kebede, Nigatu; Gebre-Selassie, Solomon; Mihret, Adane; Alemayehu, Haile

2014-09-17

Typhoid fever is a major health problem in developing countries and its diagnosis on clinical ground is difficult. Diagnosis in developing countries including Ethiopia is mostly done by Widal test. However, the value of the test has been debated. Hence, evaluating the result of this test is necessary for correct interpretation of the result. The main aim of this study was to compare the result of Widal test and blood culture in the diagnosis of typhoid fever in febrile patients. Blood samples were collected from 270 febrile patients with symptoms clinically similar to typhoid fever and visiting St. Paul's General Specialized Hospitals from mid December 2010 to March 2011. Blood culture was used to isolate S.typhi and S.paratyphi. Slide agglutination test and tube agglutination tests were used for the determination of antibody titer. An antibody titer of ≥1:80 for anti TO and ≥1:160 for anti TH were taken as a cut of value to indicate recent infection of typhoid fever. One hundred and eighty six (68.9%) participants were females and eighty four (31.1%) were males. 7 (2.6%) cases of S. typhi and 4 (1.5%) cases of S. paratyphi were identified with the total prevalence of typhoid fever 4.1%. The total number of patients who have indicative of recent infection by either of O and H antigens Widal test is 88 (32.6%). The sensitivity, specificity, Positive predictive Value and Negative predictive Value of Widal test were 71.4%, 68.44%, 5.7% and 98.9% respectively. Widal test has a low sensitivity, specificity and PPV, but it has good NPV which indicates that negative Widal test result have a good indication for the absence of the disease.

Multi-drug resistance and reduced susceptibility to ciprofloxacin among Salmonella enterica serovar Typhi isolates from the Middle East and Central Asia.

PubMed

Rahman, B A; Wasfy, M O; Maksoud, M A; Hanna, N; Dueger, E; House, B

2014-07-01

Typhoid fever is common in developing countries, with an estimated 120 million infections and 700 000 annual deaths, worldwide. Fluoroquinolones have been the treatment of choice for infection with multidrug-resistant (MDR) Salmonella enterica serovar Typhi (S. Typhi). However, alarming reports of fluoroquinolone-resistance and failure of typhoid fever treatment have recently been published. To determine the proportion of S. Typhi isolates with reduced susceptibility to ciprofloxacin (RSC) from six countries in the Middle East and Central Asia, 968 S. Typhi isolates collected between 2002 and 2007 from Egypt, Uzbekistan, Pakistan, Qatar, Jordan and Iraq were tested for antibiotic susceptibility to five antibiotics using the disc-diffusion method. MDR was defined as resistance to amicillin, chloramphenicol and trimethoprim-sulfamethoxazole. The E-test was employed to determine the MIC of ciprofloxacin only. Nalidixic acid resistance was evaluated as a marker for RSC. Interpretations were made according to CLSI guidelines. MDR strains were considerably more prevalent in Iraq (83%) and Pakistan (52%) compared with the other countries studied (13-52%). Nearly all isolates were susceptible (99.7%) to ceftriaxone. RSC was detected in a total of 218 isolates (22%), mostly from Iraq (54/59, 92%), Uzbekistan (98/123, 80%), Qatar (23/43, 54%) and Pakistan (31/65, 47%). Many of these (21%) were also MDR. Use of nalidixic acid resistance as an indicator for RSC was 99% sensitive and 98% specific. This study reinforces the need for routine antimicrobial susceptibility surveillance of enteric fever isolates and close review of current therapeutic policies in the region.

Antimicrobial resistance and management of invasive Salmonella disease.

PubMed

Kariuki, Samuel; Gordon, Melita A; Feasey, Nicholas; Parry, Christopher M

2015-06-19

Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. Copyright © 2015. Published by Elsevier Ltd.

Antimicrobial resistance and management of invasive Salmonella disease

PubMed Central

Kariuki, Samuel; Gordon, Melita A.; Feasey, Nicholas; Parry, Christopher M

2015-01-01

Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20–30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50–75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. PMID:25912288

Determination of free polysaccharide in Vi glycoconjugate vaccine against typhoid fever.

PubMed

Giannelli, C; Cappelletti, E; Di Benedetto, R; Pippi, F; Arcuri, M; Di Cioccio, V; Martin, L B; Saul, A; Micoli, F

2017-05-30

Glycoconjugate vaccines based on the Vi capsular polysaccharide directed against Salmonella enterica serovar Typhi are licensed or in development against typhoid fever, an important cause of morbidity and mortality in developing countries. Quantification of free polysaccharide in conjugate vaccines is an important quality control for release, to monitor vaccine stability and to ensure appropriate immune response. However, we found that existing separation methods based on size are not appropriate as free Vi non-specifically binds to unconjugated and conjugated protein. We developed a method based on free Vi separation by Capto Adhere resin and quantification by HPAEC-PAD. The method has been tested for conjugates of Vi derived from Citrobacter freundii with different carrier proteins such as CRM 197 , Tetanus Toxoid and Diphtheria Toxoid. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

PubMed

de Jong, Hanna K; Parry, Chris M; van der Vaart, Thomas W; Kager, Liesbeth M; van den Ende, Stannie J; Maude, Rapeephan R; Wijedoru, Lalith; Ghose, Aniruddha; Hassan, Mohammed U; Hossain, Mohammed A; Dondorp, Arjan M; Baker, Steve; Faiz, M Abul; Meijers, Joost C M; Wiersinga, W Joost

2018-05-07

Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Value of a Single-Tube Widal Test in Diagnosis of Typhoid Fever in Vietnam

PubMed Central

Parry, Christopher M.; Hoa, Nguyen Thi Tuyet; Diep, To Song; Wain, John; Chinh, Nguyen Tran; Vinh, Ha; Hien, Tran Tinh; White, Nicholas J.; Farrar, Jeremy J.

1999-01-01

The diagnostic value of an acute-phase single-tube Widal test for suspected typhoid fever was evaluated with 2,000 Vietnamese patients admitted to an infectious disease referral hospital between 1993 and 1998. Test patients had suspected typhoid fever and a blood culture positive for Salmonella typhi (n= 1,400) or Salmonella paratyphi A (n = 45). Control patients had a febrile illness for which another cause was confirmed (malaria [n = 103], dengue [n = 76], or bacteremia due to another microorganism [n = 156] or tetanus (n = 265). An O-agglutinin titer of ≥100 was found in 18% of the febrile controls and 7% of the tetanus patients. Corresponding values for H agglutinins were 8 and 1%, respectively. The O-agglutinin titer was ≥100 in 83% of the blood culture-positive typhoid fever cases, and the H-agglutinin titer was ≥100 in 67%. The disease prevalence in investigated patients in this hospital was 30.8% (95% confidence interval, 26.8 to 35.1%); at this prevalence, an elevated level of H agglutinins gave better positive predictive values for typhoid fever than did O agglutinins. With a cutoff titer of ≥200 for O agglutinin or ≥100 for H agglutinin, the Widal test would diagnose correctly 74% of the blood culture-positive cases of typhoid fever. However, 14% of the positive results would be false-positive, and 10% of the negative results would be false-negative. The Widal test can be helpful in the laboratory diagnosis of typhoid fever in Vietnam if interpreted with care. PMID:10449469

Global MLST of Salmonella Typhi Revisited in Post-genomic Era: Genetic Conservation, Population Structure, and Comparative Genomics of Rare Sequence Types.

PubMed

Yap, Kien-Pong; Ho, Wing S; Gan, Han M; Chai, Lay C; Thong, Kwai L

2016-01-01

Typhoid fever, caused by Salmonella enterica serovar Typhi, remains an important public health burden in Southeast Asia and other endemic countries. Various genotyping methods have been applied to study the genetic variations of this human-restricted pathogen. Multilocus sequence typing (MLST) is one of the widely accepted methods, and recently, there is a growing interest in the re-application of MLST in the post-genomic era. In this study, we provide the global MLST distribution of S. Typhi utilizing both publicly available 1,826 S. Typhi genome sequences in addition to performing conventional MLST on S. Typhi strains isolated from various endemic regions spanning over a century. Our global MLST analysis confirms the predominance of two sequence types (ST1 and ST2) co-existing in the endemic regions. Interestingly, S. Typhi strains with ST8 are currently confined within the African continent. Comparative genomic analyses of ST8 and other rare STs with genomes of ST1/ST2 revealed unique mutations in important virulence genes such as flhB, sipC, and tviD that may explain the variations that differentiate between seemingly successful (widespread) and unsuccessful (poor dissemination) S. Typhi populations. Large scale whole-genome phylogeny demonstrated evidence of phylogeographical structuring and showed that ST8 may have diverged from the earlier ancestral population of ST1 and ST2, which later lost some of its fitness advantages, leading to poor worldwide dissemination. In response to the unprecedented increase in genomic data, this study demonstrates and highlights the utility of large-scale genome-based MLST as a quick and effective approach to narrow the scope of in-depth comparative genomic analysis and consequently provide new insights into the fine scale of pathogen evolution and population structure.

The Ecological Dynamics of Fecal Contamination and Salmonella Typhi and Salmonella Paratyphi A in Municipal Kathmandu Drinking Water

PubMed Central

Walker, Alan W.; Thompson, Corinne N.; Torres, Andres; Dongol, Sabina; Tran Vu Thieu, Nga; Pham Thanh, Duy; Tran Thi Ngoc, Dung; Voong Vinh, Phat; Singer, Andrew C.; Parkhill, Julian; Thwaites, Guy; Basnyat, Buddha; Ferguson, Neil; Baker, Stephen

2016-01-01

One of the UN sustainable development goals is to achieve universal access to safe and affordable drinking water by 2030. It is locations like Kathmandu, Nepal, a densely populated city in South Asia with endemic typhoid fever, where this goal is most pertinent. Aiming to understand the public health implications of water quality in Kathmandu we subjected weekly water samples from 10 sources for one year to a range of chemical and bacteriological analyses. We additionally aimed to detect the etiological agents of typhoid fever and longitudinally assess microbial diversity by 16S rRNA gene surveying. We found that the majority of water sources exhibited chemical and bacterial contamination exceeding WHO guidelines. Further analysis of the chemical and bacterial data indicated site-specific pollution, symptomatic of highly localized fecal contamination. Rainfall was found to be a key driver of this fecal contamination, correlating with nitrates and evidence of S. Typhi and S. Paratyphi A, for which DNA was detectable in 333 (77%) and 303 (70%) of 432 water samples, respectively. 16S rRNA gene surveying outlined a spectrum of fecal bacteria in the contaminated water, forming complex communities again displaying location-specific temporal signatures. Our data signify that the municipal water in Kathmandu is a predominant vehicle for the transmission of S. Typhi and S. Paratyphi A. This study represents the first extensive spatiotemporal investigation of water pollution in an endemic typhoid fever setting and implicates highly localized human waste as the major contributor to poor water quality in the Kathmandu Valley. PMID:26735696

The Ecological Dynamics of Fecal Contamination and Salmonella Typhi and Salmonella Paratyphi A in Municipal Kathmandu Drinking Water.

PubMed

Karkey, Abhilasha; Jombart, Thibaut; Walker, Alan W; Thompson, Corinne N; Torres, Andres; Dongol, Sabina; Tran Vu Thieu, Nga; Pham Thanh, Duy; Tran Thi Ngoc, Dung; Voong Vinh, Phat; Singer, Andrew C; Parkhill, Julian; Thwaites, Guy; Basnyat, Buddha; Ferguson, Neil; Baker, Stephen

2016-01-01

One of the UN sustainable development goals is to achieve universal access to safe and affordable drinking water by 2030. It is locations like Kathmandu, Nepal, a densely populated city in South Asia with endemic typhoid fever, where this goal is most pertinent. Aiming to understand the public health implications of water quality in Kathmandu we subjected weekly water samples from 10 sources for one year to a range of chemical and bacteriological analyses. We additionally aimed to detect the etiological agents of typhoid fever and longitudinally assess microbial diversity by 16S rRNA gene surveying. We found that the majority of water sources exhibited chemical and bacterial contamination exceeding WHO guidelines. Further analysis of the chemical and bacterial data indicated site-specific pollution, symptomatic of highly localized fecal contamination. Rainfall was found to be a key driver of this fecal contamination, correlating with nitrates and evidence of S. Typhi and S. Paratyphi A, for which DNA was detectable in 333 (77%) and 303 (70%) of 432 water samples, respectively. 16S rRNA gene surveying outlined a spectrum of fecal bacteria in the contaminated water, forming complex communities again displaying location-specific temporal signatures. Our data signify that the municipal water in Kathmandu is a predominant vehicle for the transmission of S. Typhi and S. Paratyphi A. This study represents the first extensive spatiotemporal investigation of water pollution in an endemic typhoid fever setting and implicates highly localized human waste as the major contributor to poor water quality in the Kathmandu Valley.

Typhoid fever causing haemophagocytic lymphohistiocytosis in a non-endemic country - first case report and review of the current literature.

PubMed

Sánchez-Moreno, Paula; Olbrich, Peter; Falcón-Neyra, Lola; Lucena, Jose Manuel; Aznar, Javier; Neth, Olaf

2018-06-07

Development of secondary haemophagocytic lymphohistiocytosis (sHLH) in the context of typhoid fever (TF) is a very rare but serious complication. Description of the first pediatric case of typhoid fever acquired in a non-endemic area complicated by sHLH. A systematic literature review of sHLH in the context of TF was performed with extraction of epidemiological, clinical and laboratory data. The literature search revealed 17 articles (22 patients). Fifteen patients were eligible for data analysis (53.4% children). All patients had fever and pancytopenia. Transaminases and LDH were frequently elevated (46.6%). Salmonella typhi was detected mainly by blood culture (64.3%). All the patients received antibiotics whereas immunomodulation (dexamethasone) was used in two cases. A high suspicion index for this condition is needed even in non-endemic areas. The addition of immunmodulation to standard antimicrobial therapy should be considered in selected cases. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Vi Capsular Polysaccharide Produced by Recombinant Salmonella enterica Serovar Paratyphi A Confers Immunoprotection against Infection by Salmonella enterica Serovar Typhi

PubMed Central

Xiong, Kun; Zhu, Chunyue; Chen, Zhijin; Zheng, Chunping; Tan, Yong; Rao, Xiancai; Cong, Yanguang

2017-01-01

Enteric fever is predominantly caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A, and accounts for an annual global incidence of 26.9 millions. In recent years, the rate of S. Paratyphi A infection has progressively increased. Currently licensed vaccines for typhoid fever, live Ty21a vaccine, Vi subunit vaccine, and Vi-conjugate vaccine, confer inadequate cross immunoprotection against enteric fever caused by S. Paratyphi A. Therefore, development of bivalent vaccines against enteric fever is urgently required. The immunogenic Vi capsular polysaccharide is characteristically produced in S. Typhi, but it is absent in S. Paratyphi A. We propose that engineering synthesis of Vi in S. Paratyphi A live-attenuated vaccine may expand its protection range to cover S. Typhi. In this study, we cloned the viaB locus, which contains 10 genes responsible for Vi biosynthesis, and integrated into the chromosome of S. Paratyphi A CMCC 50093. Two virulence loci, htrA and phoPQ, were subsequently deleted to achieve a Vi-producing attenuated vaccine candidate. Our data showed that, despite more than 200 passages, the viaB locus was stably maintained in the chromosome of S. Paratyphi A and produced the Vi polysaccharide. Nasal immunization of the vaccine candidate stimulated high levels of Vi-specific and S. Paratyphi A-specific antibodies in mice sera as well as total sIgA in intestinal contents, and showed significant protection against wild-type challenge of S. Paratyphi A or S. Typhi. Our study show that the Vi-producing attenuated S. Paratyphi A is a promising bivalent vaccine candidate for the prevention of enteric fever. PMID:28484685

[Two cases of typhoid fever with reduced susceptibility to fluoroquinolones].

PubMed

Adachi, T; Masuda, G; Imamura, A; Ajisawa, A; Negishi, M; Takayama, N; Takinaga, K; Takano, S

2001-01-01

Two separate febrile Indian patients who reside in Japan and had recently returned from their country were diagnosed as suffering from typhoid fever. Fluoroquinolone therapy was clinically ineffective and the addition of a third-generation cephalosporin was required in each case. Each strain of Salmonella Typhi was resistant to nalidixic acid in vitro and also showed higher minimal inhibitory concentration to other quinolones than usual susceptible strains. Similar cases of typhoid fever responding poorly to quinolone treatment have been observed in the Indian subcontinent, south-east Asia and central Asia since the early 1990s, and potential spread by travelers into Japan is of serious concern. Although quinolones still remain the drugs of choice for treatment of typhoid fever, physicians should be aware of the possibility and implications of clinical treatment failure.

[Breast abscess with Salmonella typhi and review of the literature].

PubMed

Delori, M; Abgueguen, P; Chennebault, J-M; Pichard, E; Fanello, S

2007-11-01

We report the case of a 54-year-old woman who presented with breast abscess, which appeared through a common alimentary toxi-infection with Salmonella Typhi, infection, which implied twelve patients having attended the same restaurant. With around hundred native cases a year in France, typhoid fever is not a very frequent toxi-infection. Among the known extra-intestinal manifestations of Salmonella infections, the breast abscess remains rare and the literature revealed less than ten published cases, including some revealed the disease. In our observation, the imputability of S. Typhi was retained based on the chronology of the clinical signs, specific treatments, and the successful outcome under antibiotherapy, in spite of the negativity of the breast abscess bacteriological samples. We also analyze rare cases of breast abscess due to S. Typhi found in the literature.

Feverlike Temperature is a Virulence Regulatory Cue Controlling the Motility and Host Cell Entry of Typhoidal Salmonella.

PubMed

Elhadad, Dana; McClelland, Michael; Rahav, Galia; Gal-Mor, Ohad

2015-07-01

Human infection with typhoidal Salmonella serovars causes a febrile systemic disease, termed enteric fever. Here we establish that in response to a temperature equivalent to fever (39 °C-42 °C) Salmonella enterica serovars Typhi, Paratyphi A, and Sendai significantly attenuate their motility, epithelial cell invasion, and uptake by macrophages. Under these feverlike conditions, the residual epithelial cell invasion of S. Paratyphi A occurs in a type III secretion system (T3SS) 1-independent manner and results in restrained disruption of epithelium integrity. The impaired motility and invasion are associated with down-regulation of T3SS-1 genes and class II and III (but not I) of the flagella-chemotaxis regulon. In contrast, we demonstrate up-regulation of particular Salmonella pathogenicity island 2 genes (especially spiC) and increased intraepithelial growth in a T3SS-2-dependent manner. These results indicate that elevated physiological temperature is a novel cue controlling virulence phenotypes in typhoidal serovars, which is likely to play a role in the distinct clinical manifestations elicited by typhoidal and nontyphoidal salmonellae. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Amplification of ST50 gene using dry-reagent-based polymerase chain reaction for the detection of Salmonella typhi.

PubMed

Aziah, Ismail; Ravichandran, Manickam; Ismail, Asma

2007-12-01

Conventional polymerase chain reaction (PCR) testing requires many pipetting steps and has to be transported and stored in cold chain. To overcome these limitations, we designed a ready-to-use PCR test for Salmonella typhi using PCR reagents, primers against the ST50 gene of S. typhi, a built-in internal amplification control (IAC), and gel loading dye mixed and freeze-dried in a single tube. The 2-step dry-reagent-based assay was used to amplify a 1238-bp target gene and an 810-bp IAC gene from 73 BACTEC blood culture broths (33 true positives for S. typhi and 40 true negatives for non-S. typhi). The sensitivity, specificity, positive predictive value, and negative predictive value of the PCR assay were 87.9%, 100%, 100%, and 90.9%, respectively. We suggest that this rapid 2-step PCR test could be used for the rapid diagnosis of typhoid fever.

Comparative study of dot enzyme immunoassay (Typhidot-M) and Widal test in the diagnosis of typhoid fever.

PubMed

Narayanappa, D; Sripathi, Rachana; Jagdishkumar, K; Rajani, H S

2010-04-01

We compared the sensitivity and specificity of Typhidot-M and Widal test with blood culture (gold standard) for diagnosing typhoid fever in 105 children aged 1-15 years admitted with clinical suspicion of typhoid fever. Of the 105 cases, blood culture was positive for S.typhi in 41 (39%) children, Widal test was positive in 48 (45.7%) and Typhidot-M was positive in 78 (74.3%) cases. Sensitivity and specificity of Typhidot-M was 92.6% and 37.5% while sensitivity and specificity of Widal test was 34.1% and 42.8%, respectively. In children with fever of less than 7 days duration, Typhidot-M was positive in 97%, compared to 24.2% by Widal test. Typhidot-M is a simple and sensitive test for early diagnosis of typhoid fever in children.

Antibacterial activities of Origanum vulgare alone and in combination with different antimicrobials against clinical isolates of Salmonella typhi

PubMed Central

Bharti, Veni; Vasudeva, Neeru; Sharma, Sunil; Duhan, Joginder Singh

2013-01-01

Background: Typhoid fever continues to remain a major public health problem especially in the areas where there is problem of sanitation and hygiene. The emergence of multidrug resistance of Salmonella typhi, the bacteria responsible for Typhoid to ampicillin, chloramphenicol, and cotrimoxazole has further complicated the treatment and management of enteric fever. One strategy for the treatment of the multidrug resistant bacteria is to use herbs in combination with conventional drugs. The present study was done to find out the interaction effect of phenolic, nonphenolic fractions, and volatile oil of Origanum vulgare with ciprofloxacin. Materials and Methods: The minimum inhibitory concentration (MIC) by microdilution method for individual phytoconstituents and in combination with ciprofloxacin was compared for clinically isolated bacteria from patients infected with S. typhi. Fractional inhibitory concentration (FIC) and Fractional inhibitory concentration index (FICI) were also calculated. Results: The MIC declined to a significant level indicating synergistic relationship between ciprofloxacin and phenolic, nonphenolic fractions and volatile oil in vitro. The FICI exhibits synergistic effect for all the three samples while indifferent and antagonistic for samples and for phenolic and nonphenolic fractions. Conclusions: Present study shows that not only the formulation using O. vulgare and ciprofloxacin can overcome multidrug resistance but also will reduce the toxic effects of ciprofloxacin. PMID:24991069

Prevalence of current patterns and predictive trends of multidrug-resistant Salmonella Typhi in Sudan.

PubMed

Elshayeb, Ayman A; Ahmed, Abdelazim A; El Siddig, Marmar A; El Hussien, Adil A

2017-11-14

Enteric fever has persistence of great impact in Sudanese public health especially during rainy season when the causative agent Salmonella enterica serovar Typhi possesses pan endemic patterns in most regions of Sudan - Khartoum. The present study aims to assess the recent state of antibiotics susceptibility of Salmonella Typhi with special concern to multidrug resistance strains and predict the emergence of new resistant patterns and outbreaks. Salmonella Typhi strains were isolated and identified according to the guidelines of the International Standardization Organization and the World Health Organization. The antibiotics susceptibilities were tested using the recommendations of the Clinical Laboratories Standards Institute. Predictions of emerging resistant bacteria patterns and outbreaks in Sudan were done using logistic regression, forecasting linear equations and in silico simulations models. A total of 124 antibiotics resistant Salmonella Typhi strains categorized in 12 average groups were isolated, different patterns of resistance statistically calculated by (y = ax - b). Minimum bactericidal concentration's predication of resistance was given the exponential trend (y = n e x ) and the predictive coefficient R 2  > 0 < 1 are approximately alike. It was assumed that resistant bacteria occurred with a constant rate of antibiotic doses during the whole experimental period. Thus, the number of sensitive bacteria decreases at the same rate as resistant occur following term to the modified predictive model which solved computationally. This study assesses the prediction of multi-drug resistance among S. Typhi isolates by applying low cost materials and simple statistical methods suitable for the most frequently used antibiotics as typhoid empirical therapy. Therefore, bacterial surveillance systems should be implemented to present data on the aetiology and current antimicrobial drug resistance patterns of community-acquired agents causing outbreaks.

Challenges and Opportunities for Typhoid Fever Control: A Call for Coordinated Action

PubMed Central

Steele, A. Duncan; Hay Burgess, Deborah C.; Diaz, Zoey; Carey, Megan E.; Zaidi, Anita K. M.

2016-01-01

The burden of enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi is substantial and has high impact in toddlers and young children. This burden is relatively well documented in Asia, and this supplement provides new data on the substantial burden in several sub-Saharan African countries. Challenges in standardized surveillance and imperfect diagnostic tools have resulted in patchy local disease data, which are not well acknowledged or integrated into local country evidence and health awareness for decision making. There is a need to strengthen diagnostics for the generation of burden data in country. Furthermore, the guidelines and training for treatment of enteric fever cases in Africa are sorely needed to help mitigate the inappropriate use of antimicrobial treatment. Classic water safety and access to sanitation development remain powerful tools for the control of typhoid fever, yet the huge economic costs and long timelines are unlikely to provide a short- to middle-term solution. Emerging threats, including multidrug resistance and increasing urbanization in regions such as sub-Saharan Africa, warrant focused attention to shorter-term interventions including immunization, and must include vaccine strategies with the new typhoid conjugate vaccines. PMID:26933019

[Typhoid fever in school children: by what measures is the modification of the clinical course due to oral vaccination?].

PubMed

Contreras, R; Ferreccio, C; Sotomayor, V; Astroza, L; Berríos, G; Ortiz, E; Palomino, C; Prenzel, I; Pinto, M E; Levine, M

1992-02-01

The clinical course of infection by Salmonellae was compared between patients who had been vaccinated against typhoid fever using the Ty21a vaccine and those who had not. Of 2566 bacteriological confirmed cases 84% were infected with S typhi, 14% with S paratyphi B and 2% with S paratyphi A. Among patients with typhoid fever, 34% were treated in hospital, 3.5% had relapses, 5.4% developed complications and 1 patient died (0.05%). Among patients with paratyphoid fever, 18% were treated in hospital, 0.6% had relapses, 1.4% developed complications and there were no deaths. These figures were similar among vaccinated and non-vaccinated cases. A slightly greater proportion of vaccinated cases were treated in hospital (38 vs 30%). Thus, use of oral vaccination against typhoid fever does not alter the clinical course of infection with Salmonellae.

Comparative genomics of closely related Salmonella enterica serovar Typhi strains reveals genome dynamics and the acquisition of novel pathogenic elements.

PubMed

Yap, Kien-Pong; Gan, Han Ming; Teh, Cindy Shuan Ju; Chai, Lay Ching; Thong, Kwai Lin

2014-11-20

Typhoid fever is an infectious disease of global importance that is caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi). This disease causes an estimated 200,000 deaths per year and remains a serious global health threat. S. Typhi is strictly a human pathogen, and some recovered individuals become long-term carriers who continue to shed the bacteria in their faeces, thus becoming main reservoirs of infection. A comparative genomics analysis combined with a phylogenomic analysis revealed that the strains from the outbreak and carrier were closely related with microvariations and possibly derived from a common ancestor. Additionally, the comparative genomics analysis with all of the other completely sequenced S. Typhi genomes revealed that strains BL196 and CR0044 exhibit unusual genomic variations despite S. Typhi being generally regarded as highly clonal. The two genomes shared distinct chromosomal architectures and uncommon genome features; notably, the presence of a ~10 kb novel genomic island containing uncharacterised virulence-related genes, and zot in particular. Variations were also detected in the T6SS system and genes that were related to SPI-10, insertion sequences, CRISPRs and nsSNPs among the studied genomes. Interestingly, the carrier strain CR0044 harboured far more genetic polymorphisms (83% mutant nsSNPs) compared with the closely related BL196 outbreak strain. Notably, the two highly related virulence-determinant genes, rpoS and tviE, were mutated in strains BL196 and CR0044, respectively, which revealed that the mutation in rpoS is stabilising, while that in tviE is destabilising. These microvariations provide novel insight into the optimisation of genes by the pathogens. However, the sporadic strain was found to be far more conserved compared with the others. The uncommon genomic variations in the two closely related BL196 and CR0044 strains suggests that S. Typhi is more diverse than previously thought. Our study has demonstrated that the pathogen is continually acquiring new genes through horizontal gene transfer in the process of host adaptation, providing novel insight into its unusual genomic dynamics. The understanding of these strains and virulence factors, and particularly the strain that is associated with the large outbreak and the less studied asymptomatic Typhi carrier in the population, will have important impact on disease control.

Detection of urinary Vi antigen as a diagnostic test for typhoid fever.

PubMed Central

Taylor, D N; Harris, J R; Barrett, T J; Hargrett, N T; Prentzel, I; Valdivieso, C; Palomino, C; Levine, M M; Blake, P A

1983-01-01

Since Vi antigen is limited primarily to Salmonella typhi, it has been thought that detection of the antigen may be a useful method for diagnosing acute typhoid fever. The slide coagglutination method and enzyme-linked immunosorbent assay have recently been suggested as ways to detect small quantities of Vi antigen in urine. In Santiago, Chile, we compared the results of these two methods in patients with acute typhoid fever, paratyphoid fever, and other febrile illnesses and in afebrile control subjects. Using a cut-off value that maximally separated typhoid patients from controls, the enzyme-linked immunosorbent assay was positive in 62.4% of 141 patients with culture-proven typhoid infections and in 13.2% of 159 afebrile control subjects. The enzyme-linked immunosorbent assay was false positive in 64.7% of 34 culture-proven paratyphoid A or B patients and 47.1% of 21 patients with other nontyphoidal febrile illnesses. The coagglutination test was positive in 34% of typhoid patients, 14% of afebrile control subjects, and 46% of febrile control subjects. We conclude that these tests when performed with the Vi antibodies employed in this study are of little value for the diagnosis of typhoid fever in this setting. PMID:6630465

Chromosomal Rearrangements in Salmonella enterica Serotype Typhi Affecting Molecular Typing in Outbreak Investigations

PubMed Central

Echeita, M. A.; Usera, M. A.

1998-01-01

Salmonella enterica serotype Typhi strains belonging to eight different outbreaks of typhoid fever that occurred in Spain between 1989 and 1994 were analyzed by ribotyping and pulsed-field gel electrophoresis. For three outbreaks, two different patterns were detected for each outbreak. The partial digestion analysis by the intron-encoded endonuclease I-CeuI of the two different strains from each outbreak provided an excellent tool for examining the organization of the genomes of epidemiologically related strains. S. enterica serotype Typhi seems to be more susceptible than other serotypes to genetic rearrangements produced by homologous recombinations between rrn operons; these rearrangements do not substantially alter the stability or survival of the bacterium. We conclude that genetic rearrangements can occur during the emergence of an outbreak. PMID:9650981

Risk factors for typhoid outbreak in Sungai Congkak Recreational Park, Selangor 2009.

PubMed

Anita, S; Amir, K M; Fadzilah, K; Ahamad, J; Noorhaida, U; Marina, K; Paid, M Y; Hanif, Z

2012-02-01

Typhoid fever continues to pose public health problems in Selangor where cases are found sporadically with occasional outbreaks reported. In February 2009, Hospital Tengku Ampuan Rahimah (HTAR) reported a cluster of typhoid fever among four children in the pediatric ward. We investigated the source of the outbreak, risk factors for the infection to propose control measures. We conducted a case-control study to identify the risk factors for the outbreak. A case was defined as a person with S. typhi isolated from blood, urine or stool and had visited Sungai Congkak recreational park on 27th January 2010. Controls were healthy household members of cases who have similar exposure but no isolation of S. typhi in blood, urine or stool. Cases were identified from routine surveillance system, medical record searching from the nearest clinic and contact tracing other than family members including food handlers and construction workers in the recreational park. Immediate control measures were initiated and followed up. Twelve (12) cases were identified from routine surveillance with 75 household controls. The Case-control study showed cases were 17 times more likely to be 12 years or younger (95% CI: 2.10, 137.86) and 13 times more likely to have ingested river water accidentally during swimming (95% CI: 3.07, 58.71). River water was found contaminated with sewage disposal from two public toilets which effluent grew salmonella spp. The typhoid outbreak in Sungai Congkak recreational park resulted from contaminated river water due to poor sanitation. Children who accidentally ingested river water were highly susceptible. Immediate closure and upgrading of public toilet has stopped the outbreak.

Resistance Patterns of Typhoid Fever in Children: A Longitudinal Community-Based Study.

PubMed

Vala, Snehal; Shah, Urvesh; Ahmad, Syed Amir; Scolnik, Dennis; Glatstein, Miguel

2016-01-01

Salmonella typhi and S. paratyphi are important causes of bacteremia in children, especially those from the developing world. There is a lack of standardized treatment protocols for such patients in the literature, and there are also reports of therapeutic failure related to resistance to commonly used antibiotics. We analyzed the epidemiological, clinical, and antimicrobiological sensitivity patterns of disease in patients diagnosed with blood culture-positive typhoid fever over a 6-month period in a tertiary-care pediatric hospital in western India. Data were retrospectively analyzed for all patients with Salmonella isolates on blood culture between January 1 and June 30, 2011 at the Synergy Neonatal and Pediatric Hospital. Susceptibility of isolates to antimicrobials and minimum inhibitory concentrations were determined. Demographic data, symptoms and signs, basic laboratory results, treatment courses, and clinical outcomes were collected from clinical charts. All of the 61 isolates of S. typhi were sensitive to cefepime (fourth-generation cephalosporin), 96% to third-generation cephalosporins, and 95% to quinolones. There was intermediate sensitivity to ampicillin (92%) and chloramphenicol (80%). Notably, azithromycin resistance was observed in 63% of isolates. All patients ultimately made full recoveries. There is an urgent need for large scale, community-based clinical trials to evaluate the effectiveness of different antibiotics in enteric fever. Our antimicrobial susceptibility data suggest that quinolones and third-generation cephalosporins should be used as first-line antimicrobials in enteric fever. Although fourth-generation cephalosporins are useful, we feel their use should be restricted to complicated or resistant cases.

An international point source outbreak of typhoid fever: a European collaborative investigation*

PubMed Central

Stanwell-Smith, R. E.; Ward, L. R.

1986-01-01

A point source outbreak of Salmonella typhi, degraded Vi-strain 22, affecting 32 British visitors to Kos, Greece, in 1983 was attributed by a case—control study to the consumption of a salad at one hotel. This represents the first major outbreak of typhoid fever in which a salad has been identified as the vehicle. The source of the infection was probably a carrier in the hotel staff. The investigation demonstrates the importance of national surveillance, international cooperation, and epidemiological methods in the investigation and control of major outbreaks of infection. PMID:3488842

Immunity to Salmonella typhi: considerations relevant to measurement of cellular immunity in typhoid-endemic regions.

PubMed Central

Murphy, J R; Wasserman, S S; Baqar, S; Schlesinger, L; Ferreccio, C; Lindberg, A A; Levine, M M

1989-01-01

Experiments were performed in Baltimore, Maryland and in Santiago, Chile, to determine the level of Salmonella typhi antigen-driven in vitro lymphocyte replication response which signifies specific acquired immunity to this bacterium and to determine the best method of data analysis and form of data presentation. Lymphocyte replication was measured as incorporation of 3H-thymidine into desoxyribonucleic acid. Data (ct/min/culture) were analyzed in raw form and following log transformation, by non-parametric and parametric statistical procedures. A preference was developed for log-transformed data and discriminant analysis. Discriminant analysis of log-transformed data revealed 3H-thymidine incorporation rates greater than 3,433 for particulate S. typhi, Ty2 antigen stimulated cultures signified acquired immunity at a sensitivity and specificity of 82.7; for soluble S. typhi O polysaccharide antigen-stimulated cultures, ct/min/culture values of greater than 1,237 signified immunity (sensitivity and specificity 70.5%). PMID:2702777

Risk reduction assessment of waterborne Salmonella and Vibrio by a chlorine contact disinfectant point-of-use device.

PubMed

Coulliette, Angela D; Enger, Kyle S; Weir, Mark H; Rose, Joan B

2013-06-01

Unsafe drinking water continues to burden developing countries despite improvements in clean water delivery and sanitation, in response to Millennium Development Goal 7. Salmonella serotype Typhi and Vibrio cholerae bacteria can contaminate drinking water, causing waterborne typhoid fever and cholera, respectively. Household water treatment (HWT) systems are widely promoted to consumers in developing countries but it is difficult to establish their benefits to the population for specific disease reduction. This research uses a laboratory assessment of halogenated chlorine beads treating contaminated water to inform a quantitative microbial risk assessment (QMRA) of S. Typhi and V. cholerae disease in a developing country community of 1000 people. Laboratory challenges using seeded well water resulted in log10 reductions of 5.44 (± 0.98 standard error (SE)) and 6.07 (± 0.09 SE) for Salmonella serotype Typhimurium and V. cholerae, respectively. In well water with 10% sewage and seeded bacteria, the log10 reductions were 6.06 (± 0.62 SE) and 7.78 (± 0.11 SE) for S. Typhimurium and V. cholerae, respectively. When one infected individual was contributing to the water contamination through fecal material leaking into the water source, the risk of disease associated with drinking untreated water was high according to a Monte Carlo analysis: a median of 0.20 (interquartile range [IQR] 0.017-0.54) for typhoid fever and a median of 0.11 (IQR 0.039-0.20) for cholera. If water was treated, risk greatly decreased, to a median of 4.1 × 10(-7) (IQR 1.6 × 10(-8) to 1.1 × 10(-5)) for typhoid fever and a median of 3.5 × 10(-9) (IQR 8.0 × 10(-10) to 1.3 × 10(-8)) for cholera. Insights on risk management policies and strategies for public health workers were gained using a simple QMRA scenario informed by laboratory assessment of HWT. Copyright © 2012 Elsevier GmbH. All rights reserved.

Integration of molecular dynamics simulation and hotspot residues grafting for de novo scFv design against Salmonella Typhi TolC protein.

PubMed

Leong, Siew Wen; Lim, Theam Soon; Ismail, Asma; Choong, Yee Siew

2018-05-01

With the development of de novo binders for protein targets from non-related scaffolds, many possibilities for therapeutics and diagnostics have been created. In this study, we described the use of de novo design approach to create single-chain fragment variable (scFv) for Salmonella enterica subspecies enterica serovar Typhi TolC protein. Typhoid fever is a global health concern in developing and underdeveloped countries. Rapid typhoid diagnostics will improve disease management and therapy. In this work, molecular dynamics simulation was first performed on a homology model of TolC protein in POPE membrane bilayer to obtain the central structure that was subsequently used as the target for scFv design. Potential hotspot residues capable of anchoring the binders to the target were identified by docking "disembodied" amino acid residues against TolC surface. Next, scFv scaffolds were selected from Protein Data Bank to harbor the computed hotspot residues. The hotspot residues were then incorporated into the scFv scaffold complementarity determining regions. The designs recapitulated binding energy, shape complementarity, and interface surface area of natural protein-antibody interfaces. This approach has yielded 5 designs with high binding affinity against TolC that may be beneficial for the future development of antigen-based detection agents for typhoid diagnostics. Copyright © 2017 John Wiley & Sons, Ltd.

Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever

PubMed Central

Wijedoru, Lalith; Mallett, Sue; Parry, Christopher M

2017-01-01

Background Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. Objectives To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. Selection criteria We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Data collection and analysis Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. Main results Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75% (median prevalence 24%, interquartile range (IQR) 11% to 46%). The included studies evaluated 16 different RDTs, and 16 studies compared two or more different RDTs. Only three studies used the Grade 1 reference standard, and only 11 studies recruited unselected febrile patients. Most included studies were from Asia, with five studies from sub-Saharan Africa. All of the RDTs were designed to detect S.Typhi infection only. Most studies evaluated three RDTs and their variants: TUBEX in 14 studies; Typhidot (Typhidot, Typhidot-M, and TyphiRapid-Tr02) in 22 studies; and the Test-It Typhoid immunochromatographic lateral flow assay, and its earlier prototypes (dipstick, latex agglutination) developed by the Royal Tropical Institute, Amsterdam (KIT) in nine studies. Meta-analyses showed an average sensitivity of 78% (95% confidence interval (CI) 71% to 85%) and specificity of 87% (95% CI 82% to 91%) for TUBEX; and an average sensitivity of 69% (95% CI 59% to 78%) and specificity of 90% (95% CI 78% to 93%) for all Test-It Typhoid and prototype tests (KIT). Across all forms of the Typhidot test, the average sensitivity was 84% (95% CI 73% to 91%) and specificity was 79% (95% CI 70% to 87%). When we based the analysis on the 13 studies of the Typhidot test that either reported indeterminate test results or where the test format means there are no indeterminate results, the average sensitivity was 78% (95% CI 65% to 87%) and specificity was 77% (95% CI 66% to 86%). We did not identify any difference in either sensitivity or specificity between TUBEX, Typhidot, and Test-it Typhoid tests when based on comparison to the 13 Typhidot studies where indeterminate results are either reported or not applicable. If TUBEX and Test-it Typhoid are compared to all Typhidot studies, the sensitivity of Typhidot was higher than Test-it Typhoid (15% (95% CI 2% to 28%), but other comparisons did not show a difference at the 95% level of CIs. In a hypothetical cohort of 1000 patients presenting with fever where 30% (300 patients) have enteric fever, on average Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results will miss the diagnosis in 66 patients with enteric fever, TUBEX will miss 66, and Test-It Typhoid and prototype (KIT) tests will miss 93. In the 700 people without enteric fever, the number of people incorrectly diagnosed with enteric fever would be 161 with Typhidot tests, 91 with TUBEX, and 70 with Test-It Typhoid and prototype (KIT) tests. The CIs around these estimates were wide, with no difference in false positive results shown between tests. The quality of the data for each study was evaluated using a standardized checklist called QUADAS-2. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. Authors' conclusions In 37 studies that evaluated the diagnostic accuracy of RDTs for enteric fever, few studies were at a low risk of bias. The three main RDT tests and variants had moderate diagnostic accuracy. There was no evidence of a difference between the average sensitivity and specificity of the three main RDT tests. More robust evaluations of alternative RDTs for enteric fever are needed. The accuracy of rapid diagnostic tests for detecting typhoid and paratyphoid (enteric) fever Cochrane researchers assessed the accuracy of commercially-available rapid diagnostic tests and their prototypes (including TUBEX, Typhidot, Typhidot-M, Test-it Typhoid, and other tests) for detecting typhoid and paratyphoid (enteric) fever in people living in countries where the estimated number of individuals with the disease at any one time is greater than 10 per 100,000 population. If accurate, they could replace the current World Health Organization (WHO)-recommended diagnostic test: culture (growing the bacteria that causes the infection from a patient’s blood or bone marrow). Background Typhoid fever and paratyphoid fever are infections caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A respectively. The term ‘enteric fever’ is used to describe both infections. Enteric fever can be difficult to diagnose as the signs and symptoms are similar to those of other infectious diseases that cause fever such as malaria. The recommended test to confirm if a person has enteric fever is to grow the Salmonella from their blood. It takes at least 48 hours to give a result, so cannot help healthcare workers make a diagnosis the same day the blood culture is taken. Blood cultures may give a negative result even though a person has enteric fever. The test also requires a laboratory and trained staff, which are often unavailable in communities where enteric fever is common. Rapid diagnostic tests (RDTs) are designed to be easy to use, and to deliver a quick result without the need for a blood culture laboratory. The cost of an enteric fever RDT would be significantly less than a blood culture, and requires less training to perform. Study characteristics Cochrane researchers searched the available literature up to 4 March 2016 and included 37 studies. Most studies recruited participants from South Asia. Most participants were adults, with 22 studies including children. All of the RDTs evaluated detected Salmonella Typhi (typhoid fever) only. Quality of the evidence The Cochrane researchers evaluated the quality of the data for each study using a standardized checklist called QUADAS-2. High quality studies that compared different types of RDT in the same patients were few in number. Two-thirds of the included studies did not evaluate the RDTs in the context of patients who are typically tested for the disease. Many studies utilized a particular study design (a case control study) which risks overestimating RDT accuracy. In the studies evaluating the Typhidot RDT, it was often unclear how many test results were indeterminate, when the test cannot distinguish a current episode of infection from a previous disease episode. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. Key results Sensitivity indicates the percentage of patients with a positive test result who are correctly diagnosed with disease. Specificity indicates the percentage of patients who are correctly identified as not having disease. TUBEX showed an average sensitivity of 78% and specificity of 87%. Typhidot studies, grouped together to include Typhidot, Typhidot-M, and TyphiRapid-Tr02, showed an average sensitivity of 84% and specificity of 79%. When Typhidot studies with clear reporting of indeterminate results are considered, the average sensitivity and specificity of Typhidot was 78% and 77% respectively. Test-It Typhoid and prototypes (KIT) showed an average sensitivity of 69% and specificity of 90%. Based on these results, in 1000 patients with fever where 30% (300 patients) have enteric fever, we would expect Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results to, on average, miss the diagnosis (give a false negative result) in 66 patients with enteric fever, TUBEX to miss 66, and Test-It Typhoid and prototypes (KIT) to miss 93. In the 700 people without enteric fever, the number of people incorrectly given a diagnosis of enteric fever (a false positive result) would be on average 161 with these Typhidot tests, 91 with TUBEX, and 70 with the Test-It Typhoid and prototypes (KIT). These differences in the number of false negative and false positive results in patients from the different tests are not statistically important. The RDTs evaluated are not sufficiently accurate to replace blood culture as a diagnostic test for enteric fever. PMID:28545155

Formation and resuscitation of viable but nonculturable Salmonella typhi.

PubMed

Zeng, Bin; Zhao, Guozhong; Cao, Xiaohong; Yang, Zhen; Wang, Chunling; Hou, Lihua

2013-01-01

Salmonella typhi is a pathogen that causes the human disease of typhoid fever. The aim of this study was to investigate the viable but nonculturable (VBNC) state of S. typhi. Some samples were stimulated at 4°C or -20°C, while others were induced by different concentrations of CuSO4. Total cell counts remained constant throughout several days by acridine orange direct counting; however, plate counts declined to undetectable levels within 48 hours by plate counting at -20°C. The direct viable counts remained fairly constant at this level by direct viable counting. Carbon and nitrogen materials slowly decreased which indicated that a large population of cells existed in the VBNC state and entered the VBNC state in response to exposure to 0.01 or 0.015 mmol/L CuSO4 for more than 14 or 12 days, respectively. Adding 3% Tween 20 or 1% catalase enabled cells to become culturable again, with resuscitation times of 48 h and 24 h, respectively. The atomic force microscope results showed that cells gradually changed in shape from short rods to coccoids, and decreased in size when they entered the VBNC state. Further animal experiments suggested that resuscitated cells might regain pathogenicity.

Antimicrobial susceptibility of travel-related Salmonella enterica serovar Typhi isolates detected in Switzerland (2002-2013) and molecular characterization of quinolone resistant isolates.

PubMed

Nüesch-Inderbinen, Magdalena; Abgottspon, Helga; Sägesser, Grethe; Cernela, Nicole; Stephan, Roger

2015-05-12

Typhoid fever is an acute, invasive, and potentially fatal systemic infection caused by Salmonella enterica subspecies enterica serotype Typhi (S. Typhi). Drug resistance to antimicrobials such as ciprofloxacin is emerging in developing countries, threatening the efficacy of treatment of patients in endemic regions as well as of travellers returning from these countries. We compared the antimicrobial resistance profiles of 192 S. Typhi isolated from patients over a time span of twelve years. Susceptibility testing was done by the disk diffusion method. A representative selection of isolates (n = 41) was screened by PCR for mutations in the quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes and all 192 isolates were screened for plasmid-mediated quinolone resistance (PMQR) genes. Multilocus sequence typing (MLST) was used to investigate the sequence type of isolates from patients with a known history of international travel. Resistance rates for nalidixic acid increased from 20 % to 66.7 % between 2002 and 2013. Resistance to ciprofloxacin was detected in 55.6 % of the isolates by 2013. Ciprofloxacin resistance was predominantly associated with the triple substitutions Ser83 → Phe and Asp87 → Asn in GyrA and Ser80 → Ile in ParC. The plasmid-mediated resistance gene qnrS1 was detected in two isolates. Sequence type ST1 was associated with the Indian subcontinent, while ST2 was distributed internationally. Multidrug resistance was noted for 11.5 % of the isolates. Fluoroquinolone resistant S. Typhi constitute a serious public health concern in endemic areas as well as in industrialized countries. Increased surveillance of global patterns of antimicrobial resistance is necessary and the control of resistant strains is of the utmost importance to maintain treatment options.

Functional assay of Salmonella typhi OmpC using reconstituted large unilamellar vesicles: a general method for characterization of outer membrane proteins.

PubMed

Sundara Baalaji, N; Mathew, M K; Krishnaswamy, S

2006-10-01

The immunodominant trimeric beta-barrel outer membrane protein OmpC from Salmonella typhi, the causative agent of typhoid, has been functionally characterized here. The activity in the vesicle environment was studied in vitro using OmpC reconstituted into proteoliposomes. Passage of polysaccharides and polyethyleneglycols through OmpC has been examined to determine the permeability properties. The relative rate of neutral solute flux yields a radius of 1.1 nm for the S. typhi OmpC pore. This is almost double the pore size of Escherichia coli. This provides an example of large pore size present in the porins that form trimers as in the general bacterial porin family. The method used in this study provides a good membrane model for functional studies of porins.

Environmental Transmission of Typhoid Fever in an Urban Slum.

PubMed

Akullian, Adam; Ng'eno, Eric; Matheson, Alastair I; Cosmas, Leonard; Macharia, Daniel; Fields, Barry; Bigogo, Godfrey; Mugoh, Maina; John-Stewart, Grace; Walson, Judd L; Wakefield, Jonathan; Montgomery, Joel M

2015-12-01

Enteric fever due to Salmonella Typhi (typhoid fever) occurs in urban areas with poor sanitation. While direct fecal-oral transmission is thought to be the predominant mode of transmission, recent evidence suggests that indirect environmental transmission may also contribute to disease spread. Data from a population-based infectious disease surveillance system (28,000 individuals followed biweekly) were used to map the spatial pattern of typhoid fever in Kibera, an urban informal settlement in Nairobi Kenya, between 2010-2011. Spatial modeling was used to test whether variations in topography and accumulation of surface water explain the geographic patterns of risk. Among children less than ten years of age, risk of typhoid fever was geographically heterogeneous across the study area (p = 0.016) and was positively associated with lower elevation, OR = 1.87, 95% CI (1.36-2.57), p <0.001. In contrast, the risk of typhoid fever did not vary geographically or with elevation among individuals more than ten years of age [corrected]. Our results provide evidence of indirect, environmental transmission of typhoid fever among children, a group with high exposure to fecal pathogens in the environment. Spatially targeting sanitation interventions may decrease enteric fever transmission.

Environmental Transmission of Typhoid Fever in an Urban Slum

PubMed Central

Matheson, Alastair I.; Cosmas, Leonard; Macharia, Daniel; Fields, Barry; Bigogo, Godfrey; Mugoh, Maina; John-Stewart, Grace; Walson, Judd L.; Wakefield, Jonathan; Montgomery, Joel M.

2015-01-01

Background Enteric fever due to Salmonella Typhi (typhoid fever) occurs in urban areas with poor sanitation. While direct fecal-oral transmission is thought to be the predominant mode of transmission, recent evidence suggests that indirect environmental transmission may also contribute to disease spread. Methods Data from a population-based infectious disease surveillance system (28,000 individuals followed biweekly) were used to map the spatial pattern of typhoid fever in Kibera, an urban informal settlement in Nairobi Kenya, between 2010–2011. Spatial modeling was used to test whether variations in topography and accumulation of surface water explain the geographic patterns of risk. Results Among children less than ten years of age, risk of typhoid fever was geographically heterogeneous across the study area (p = 0.016) and was positively associated with lower elevation, OR = 1.87, 95% CI (1.36–2.57), p <0.001. In contrast, the risk of typhoid fever did not vary geographically or with elevation among individuals less than 6b ten years of age. Conclusions Our results provide evidence of indirect, environmental transmission of typhoid fever among children, a group with high exposure to fecal pathogens in the environment. Spatially targeting sanitation interventions may decrease enteric fever transmission. PMID:26633656

Comparison of the Performance of the TPTest, Tubex, Typhidot and Widal Immunodiagnostic Assays and Blood Cultures in Detecting Patients with Typhoid Fever in Bangladesh, Including Using a Bayesian Latent Class Modeling Approach.

PubMed

Islam, Kamrul; Sayeed, Md Abu; Hossen, Emran; Khanam, Farhana; Charles, Richelle C; Andrews, Jason; Ryan, Edward T; Qadri, Firdausi

2016-04-01

There is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot. For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer ≥1:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis. Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6% (90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot. These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives.

International reference preparations of typhoid vaccine

PubMed Central

Melikova, E. N.; Lesnjak, S. V.

1967-01-01

International collaborative laboratory studies on the International Reference Preparations of Typhoid Vaccine have so far failed to provide data on which international units for these vaccines can be based. Further assays carried out using the active mouse protection test, with immunization by the subcutaneous, intraperitoneal or intravenous route, confirmed the findings by some workers that the International Reference Preparation of Typhoid Vaccine (Acetone-Inactivated) (vaccine K) was more effective than the International Reference Preparation of Typhoid Vaccine (Heat-Phenol-Inactivated) (vaccine L), and indicated that intraperitoneal immunization was the most promising method. Vaccine K, together with the material extracted by the acetone in the preparation of the vaccine, had a significantly lower effectiveness (at the 5% probability level) only when intraperitoneal immunization was used. The reasons for the differences found between the various vaccines and routes of immunization are discussed at length. It is suggested that challenge with a strain of Salmonella moscow instead of the strain of Salm. typhi used until now gives a true infection and forms the basis of a reliable method for the potency assay of typhoid vaccines. PMID:5301738

Molecular typing of Salmonella enterica serovar typhi.

PubMed Central

Navarro, F; Llovet, T; Echeita, M A; Coll, P; Aladueña, A; Usera, M A; Prats, G

1996-01-01

The efficiencies of different tests for epidemiological markers--phage typing, ribotyping, IS200 typing, and pulsed-field gel electrophoresis (PFGE)--were evaluated for strains from sporadic cases of typhoid fever and a well-defined outbreak. Ribotyping and PFGE proved to be the most discriminating. Both detected two different patterns among outbreak-associated strains. PMID:8897193

Restaurant-associated outbreak of Salmonella typhi in Nauru: an epidemiological and cost analysis.

PubMed Central

Olsen, S. J.; Kafoa, B.; Win, N. S.; Jose, M.; Bibb, W.; Luby, S.; Waidubu, G.; O'Leary, M.; Mintz, E.

2001-01-01

Typhoid fever is endemic in the South Pacific. We investigated an outbreak in Nauru. Through interviews and medical records, we identified 50 persons with onset between 1 October 1998 and 10 May 1999, of fever lasting > or = 3 days and one other symptom. Salmonella Typhi was isolated from 19 (38%) cases. Thirty-two (64%) patients were school-aged children, and 17 (34%) were in four households. Case-control studies of (a) culture-confirmed cases and age- and neighbourhood-matched controls; and (b) household index cases and randomly selected age-matched controls implicated two restaurants: Restaurant M (matched OR [MOR] = 11, 95% confidence interval [CI] = 1.3-96) and Restaurant I (MOR = 5.8, 95% CI = 1.2-29). Food-handlers at both restaurants had elevated anti-Vi antibody titres indicative of carrier state. The annual incidence was 5.0/1000 persons. Outbreak-associated costs were $46,000. Routine or emergency immunization campaigns targeting school-aged children may help prevent or control outbreaks of typhoid fever in endemic disease areas. PMID:11811872

What is the best immunization strategy for protecting African children against invasive Salmonella disease?

PubMed

Jeon, Hyon Jin; Pak, Gi Deok; Im, Justin; Owusu-Dabo, Ellis; Adu-Sarkodie, Yaw; Gassama Sow, Amy; Bassiahi, Abdramane Soura; Gasmelseed, Nagla; Keddy, Karen H; Bjerregaard-Andersen, Morten; Konings, Frank; Aseffa, Abraham; Crump, John A; Chon, Yun; Breiman, Robert F; Park, Se Eun; Cruz Espinoza, Ligia Maria; Seo, Hye Jin; May, Jürgen; Meyer, Christian G; Andrews, Jason R; Panzner, Ursula; von Kalckreuth, Vera; Wierzba, Thomas F; Rakotozandrindrainy, Raphaël; Dougan, Gordon; Levine, Myron M; Hombach, Joachim; Kim, Jerome H; Clemens, John D; Baker, Stephen; Marks, Florian

2018-05-09

The WHO recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons aged ≥6 months to 45 years residing in typhoid fever (TF)-endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations in Africa. The Typhoid Fever Surveillance in Africa Program (TSAP) in 10 sub-Saharan African countries included blood culture-based surveillance in febrile people presenting at healthcare-facilities originating from defined catchment areas. The TF/invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0-10 year-old children in yearly increments. Salmonella Typhi and iNTS were the most frequently isolated pathogens, 135 and 94 cases were identified, respectively. Isolates (12 and 4, respectively) from Ethiopia, Senegal and South Africa were excluded due to person-years of observation (PYO) data absence. 37/123 (30.1%) TF and 71/90 (78.9%) iNTS disease cases occurred among individuals aged <5 years. No TF and 8/90 (8.9%) iNTS-infections were observed in children aged <9 months. The TF incidences (/100,000 PYO) for children aged <1 year and 1-<2 years were 5 and 39, respectively; the highest incidence was 304/100,000 PYO in 4-<5 year-old children. The iNTS incidence in the defined age groups ranged between 81 and 233/100,000 PYO, with the highest incidence in 1-<2 year-old children. Higher TF/iNTS disease incidences were observed in West Africa. The high TF burden observed in TSAP merits TCV introductions. Considering the additional iNTS disease burden, a trivalent vaccine targeting S. Typhi, S. Typhimurium, and S. Enteritidis may be a future solution.

Structural and functional studies of a 50 kDa antigenic protein from Salmonella enterica serovar Typhi.

PubMed

Choong, Yee Siew; Lim, Theam Soon; Chew, Ai Lan; Aziah, Ismail; Ismail, Asma

2011-04-01

The high typhoid incidence rate in developing and under-developed countries emphasizes the need for a rapid, affordable and accessible diagnostic test for effective therapy and disease management. TYPHIDOT®, a rapid dot enzyme immunoassay test for typhoid, was developed from the discovery of a ∼50 kDa protein specific for Salmonella enterica serovar Typhi. However, the structure of this antigen remains unknown till today. Studies on the structure of this antigen are important to elucidate its function, which will in turn increase the efficiency of the development and improvement of the typhoid detection test. This paper described the predictive structure and function of the antigenically specific protein. The homology modeling approach was employed to construct the three-dimensional structure of the antigen. The built structure possesses the features of TolC-like outer membrane protein. Molecular docking simulation was also performed to further probe the functionality of the antigen. Docking results showed that hexamminecobalt, Co(NH(3))(6)(3+), as an inhibitor of TolC protein, formed favorable hydrogen bonds with D368 and D371 of the antigen. The single point (D368A, D371A) and double point (D368A and D371A) mutations of the antigen showed a decrease (single point mutation) and loss (double point mutations) of binding affinity towards hexamminecobalt. The architecture features of the built model and the docking simulation reinforced and supported that this antigen is indeed the variant of outer membrane protein, TolC. As channel proteins are important for the virulence and survival of bacteria, therefore this ∼50 kDa channel protein is a good specific target for typhoid detection test. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of ELISAs for diagnosis of acute typhoid fever in Nigerian children

PubMed Central

Felgner, Jiin; Jain, Aarti; Nakajima, Rie; Liang, Li; Jasinskas, Algis; Gotuzzo, Eduardo; Vinetz, Joseph M.; Miyajima, Fabio; Pirmohamed, Munir; Hassan-Hanga, Fatimah; Umoru, Dominic; Jibir, Binta Wudil; Gambo, Safiya; Olateju, Kudirat; Felgner, Philip L.

2017-01-01

Improved serodiagnostic tests for typhoid fever (TF) are needed for surveillance, to facilitate patient management, curb antibiotic resistance, and inform public health programs. To address this need, IgA, IgM and IgG ELISAs using Salmonella enterica serovar Typhi (S. Typhi) lipopolysaccharide (LPS) and hemolysin E (t1477) protein were conducted on 86 Nigerian pediatric TF and 29 non-typhoidal Salmonella (NTS) cases, 178 culture-negative febrile cases, 28 “other” (i.e., non-Salmonella) pediatric infections, and 48 healthy Nigerian children. The best discrimination was achieved between TF and healthy children. LPS-specific IgA and IgM provided receiver operator characteristic areas under the curve (ROC AUC) values of 0.963 and 0.968, respectively, and 0.978 for IgA+M combined. Similar performance was achieved with t1477-specific IgA and IgM (0.968 and 0.968, respectively; 0.976 combined). IgG against LPS and t1477 was less accurate for discriminating these groups, possibly as a consequence of previous exposure, although ROC AUC values were still high (0.928 and 0.932, respectively). Importantly, discrimination between TF and children with other infections was maintained by LPS-specific IgA and IgM (AUC = 0.903 and 0.934, respectively; 0.938 combined), and slightly reduced for IgG (0.909), while t1477-specific IgG performed best (0.914). A similar pattern was seen when comparing TF with other infections from outside Nigeria. The t1477 may be recognized by cross-reactive antibodies from other acute infections, although a robust IgG response may provide some diagnostic utility in populations where incidence of other infections is low, such as in children. The data are consistent with IgA and IgM against S. Typhi LPS being specific markers of acute TF. PMID:28640809

Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in Endemic Area.

PubMed

Khanna, Ashish; Khanna, Menka; Gill, Karamjit Singh

2015-11-01

Typhoid fever remains a significant health problem in endemic countries like India. Various serological tests for the diagnosis of typhoid fever are available commercially. We assessed the usefulness of rapid test based on magnetic particle separation to detect Immunoglobulin against Salmonella typhi O9 lipopolysaccharide. Aim of this study was to compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of typhoid fever in an endemic country like India. Serum samples collected from 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals residing in Amritsar were subjected to widal test, typhidot test and tubex TF test as per manufacturer's instructions. Data collected was assessed to find sensitivity and specificity of these tests in an endemic area. Significant widal test results were found positive in 68% of patients of typhoid fever and only 4% of non typhoid fever patients. Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid fever and normal healthy individuals respectively. Tubex TF showed higher sensitivity of 76% and specificity of 96-99% which was higher than typhidot and comparable to widal test. This was the first evaluation of rapid tubex TF test in northern India. In countries which can afford high cost of test, tubex TF should be recommended for the diagnosis in acute stage of the disease in clinical setting. However, there is urgent need for a highly specific and sensitive test for the diagnosis of typhoid fever in clinical settings in endemic areas.

Challenges and Opportunities for Typhoid Fever Control: A Call for Coordinated Action.

PubMed

Steele, A Duncan; Hay Burgess, Deborah C; Diaz, Zoey; Carey, Megan E; Zaidi, Anita K M

2016-03-15

The burden of enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi is substantial and has high impact in toddlers and young children. This burden is relatively well documented in Asia, and this supplement provides new data on the substantial burden in several sub-Saharan African countries. Challenges in standardized surveillance and imperfect diagnostic tools have resulted in patchy local disease data, which are not well acknowledged or integrated into local country evidence and health awareness for decision making. There is a need to strengthen diagnostics for the generation of burden data in country. Furthermore, the guidelines and training for treatment of enteric fever cases in Africa are sorely needed to help mitigate the inappropriate use of antimicrobial treatment. Classic water safety and access to sanitation development remain powerful tools for the control of typhoid fever, yet the huge economic costs and long timelines are unlikely to provide a short- to middle-term solution. Emerging threats, including multidrug resistance and increasing urbanization in regions such as sub-Saharan Africa, warrant focused attention to shorter-term interventions including immunization, and must include vaccine strategies with the new typhoid conjugate vaccines. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Mary Mallon (1869-1938) and the history of typhoid fever

PubMed Central

Marineli, Filio; Tsoucalas, Gregory; Karamanou, Marianna; Androutsos, George

2013-01-01

Mary Mallon was born in 1869 in Ireland and emigrated to the US in 1884. She had worked in a variety of domestic positions for wealthy families prior to settling into her career as a cook. As a healthy carrier of Salmonella typhi her nickname of “Typhoid Mary” had become synonymous with the spread of disease, as many were infected due to her denial of being ill. She was forced into quarantine on two separate occasions on North Brother Island for a total of 26 years and died alone without friends, having evidently found consolation in her religion to which she gave her faith and loyalty. PMID:24714738

Typhoid outbreak in Kingston, Ont: experience with high-dose oral ampicillin.

PubMed Central

Hardy, G.; Padfield, C. J.; Chadwick, P.; Partington, M. W.

1977-01-01

Twenty-four children contracted typhoid fever at a summer camp near Kingston, Ont. Six were treated with chloramphenicol alone and 15 with high doses of ampicillin (300 mg/kg-d) by mouth. Ampicillin in this dosage was well tolerated except in three children in whom severe urticarial rashes developed and two who had significant diarrhea. However, high-dose oral ampicillin therapy had no advantage over that with lower doses or over chloramphenicol as judged by the rate of defervescence after the start of treatment, the rate of clinical relapse and the frequency of excretion of Salmonella typhi during convalescence. PMID:849559

False positive malaria rapid diagnostic test in returning traveler with typhoid fever.

PubMed

Meatherall, Bonnie; Preston, Keith; Pillai, Dylan R

2014-07-09

Rapid diagnostic tests play a pivotal role in the early diagnosis of malaria where microscopy or polymerase chain reaction are not immediately available. We report the case of a 39 year old traveler to Canada who presented with fever, headache, and abdominal pain after visiting friends and relatives in India. While in India, the individual was not ill and had no signs or symptoms of malaria. Laboratory testing upon his return to Canada identified a false positive malaria rapid diagnostic (BinaxNOW® malaria) result for P. falciparum with coincident Salmonella Typhi bacteraemia without rheumatoid or autoimmune factors. Rapid diagnostic test false positivity for malaria coincided with the presence or absence of Salmonella Typhi in the blood. Clinicians should be aware that Salmonella Typhi infection may result in a false positive malaria rapid diagnostic test. The mechanism of this cross-reactivity is not clear.

Simultaneous and Rapid Detection of Salmonella typhi, Bacillus anthracis, and Yersinia pestis by Using Multiplex Polymerase Chain Reaction (PCR)

PubMed Central

Safari Foroshani, Nargess; Karami, Ali; Pourali, Fatemeh

2013-01-01

Background Salmonella typhi, Bacillus anthracis, and Yersinia pestis are some serious human pathogens, which their early diagnosis is of great importance. Salmonella typhi, Bacillus anthracis, and Yersinia pestis cause typhoid fever, anthrax, and plague respectively. These bacteria can be used to make biologic weapons. Objectives In this study, we designed a new and rapid diagnostic method based on Uniplex and Multiplex PCR method. Materials and Methods Uniplex and multiplex Polymerase Chain Reaction (PCR) were conducted on virulent genes of hp and invA of Salmonella typhimurium, Pa and chr of Bacillus anthracis, and pla of Yersinia pestis. A genome from other bacteria was used to study the specificity of the primer and the PCR test. Results Standard strains used in this study showed that primers were specific. As for sensitivity, it was shown that this method can diagnose 1-10 copies of the genome, or 1-10 Colony Forming Units (CFU) for each of the bacteria. All pieces except anthrax were sequenced in PCR to validate the product. DNA fragment resulted from Bacillus anthracis was confirmed by restriction enzyme digestions. Conclusion The designed methods are accurate, rapid, and inexpensive to find and differentiate these bacteria from similar bacteria. They can be applied for rapid diagnosis of these agents in different specimens, and bioterrorism cases. PMID:24719692

The Wisconsin State Laboratory of Hygiene and emerging enteric pathogens.

PubMed

Warshauer, David; Monson, Tim; Kurzynski, Terry

2003-01-01

At the turn of the 20th century, typhoid fever was common in Wisconsin, and was a major impetus for the establishment of the Wisconsin State Laboratory of Hygiene (WSLH) in 1903. By the 1940s, typhoid was virtually eliminated in the United States due to public health measures such as disinfection of drinking water, sewage treatment, pasteurization, and shellfish bed sanitation. However, new food and waterborne pathogens have emerged to take the place of Salmonella Typhi. Infections with non-typhoidal Salmonella strains in the United States have increased almost 10-fold since the 1950s. In the last 20 years, the emergence of foodborne pathogens, such as Escherichia coli O157:H7, Cyclospora cayetanensis, Noroviruses (Norwalk-like viruses), Cryptosporidium parvum, Campylobacter jejuni, Yersinia enterocolitica, and multi-drug-resistant Salmonella, has identified a need for accurate laboratory diagnosis of enteric disease and outbreaks.

Shifts in geographic distribution and antimicrobial resistance during a prolonged typhoid fever outbreak--Bundibugyo and Kasese Districts, Uganda, 2009-2011.

PubMed

Walters, Maroya Spalding; Routh, Janell; Mikoleit, Matthew; Kadivane, Samuel; Ouma, Caroline; Mubiru, Denis; Mbusa, Ben; Murangi, Amos; Ejoku, Emmanuel; Rwantangle, Absalom; Kule, Uziah; Lule, John; Garrett, Nancy; Halpin, Jessica; Maxwell, Nikki; Kagirita, Atek; Mulabya, Fred; Makumbi, Issa; Freeman, Molly; Joyce, Kevin; Hill, Vince; Downing, Robert; Mintz, Eric

2014-03-01

Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo. A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009-December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1-December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates. Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure, should be considered to minimize the risk of prolonged outbreaks in the future.

Shifts in Geographic Distribution and Antimicrobial Resistance during a Prolonged Typhoid Fever Outbreak — Bundibugyo and Kasese Districts, Uganda, 2009–2011

PubMed Central

Walters, Maroya Spalding; Routh, Janell; Mikoleit, Matthew; Kadivane, Samuel; Ouma, Caroline; Mubiru, Denis; Mbusa, Ben; Murangi, Amos; Ejoku, Emmanuel; Rwantangle, Absalom; Kule, Uziah; Lule, John; Garrett, Nancy; Halpin, Jessica; Maxwell, Nikki; Kagirita, Atek; Mulabya, Fred; Makumbi, Issa; Freeman, Molly; Joyce, Kevin; Hill, Vince; Downing, Robert; Mintz, Eric

2014-01-01

Background Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo. Methodology/Principal Findings A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009–December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1–December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates. Conclusions/Significance Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure, should be considered to minimize the risk of prolonged outbreaks in the future. PMID:24603860

A case of Salmonella enterica serotype typhi in a patient without a history of international travel.

PubMed

Byers, David K; Petersen, Kyle

2009-01-01

Typhoid fever, endemic in the developing world, is associated with international travel in developed nations. We present a case of Salmonella enterica infection in a patient without a history of international travel acquired from his traveling ex-wife. History of overseas travel in family members should be investigated when evaluating suspected cases.

Epidemiology and risk factors for typhoid fever in Central Division, Fiji, 2014-2017: A case-control study.

PubMed

Prasad, Namrata; Jenkins, Aaron P; Naucukidi, Lanieta; Rosa, Varanisese; Sahu-Khan, Aalisha; Kama, Mike; Jenkins, Kylie M; Jenney, Adam W J; Jack, Susan J; Saha, Debasish; Horwitz, Pierre; Jupiter, Stacy D; Strugnell, Richard A; Mulholland, E Kim; Crump, John A

2018-06-01

Typhoid fever is endemic in Fiji, with high reported annual incidence. We sought to identify the sources and modes of transmission of typhoid fever in Fiji with the aim to inform disease control. We identified and surveyed patients with blood culture-confirmed typhoid fever from January 2014 through January 2017. For each typhoid fever case we matched two controls by age interval, gender, ethnicity, and residential area. Univariable and multivariable analysis were used to evaluate associations between exposures and risk for typhoid fever. We enrolled 175 patients with typhoid fever and 349 controls. Of the cases, the median (range) age was 29 (2-67) years, 86 (49%) were male, and 84 (48%) lived in a rural area. On multivariable analysis, interrupted water availability (odds ratio [OR] = 2.17; 95% confidence interval [CI] 1.18-4.00), drinking surface water in the last 2 weeks (OR = 3.61; 95% CI 1.44-9.06), eating unwashed produce (OR = 2.69; 95% CI 1.48-4.91), and having an unimproved or damaged sanitation facility (OR = 4.30; 95% CI 1.14-16.21) were significantly associated with typhoid fever. Frequent handwashing after defecating (OR = 0.57; 95% CI 0.35-0.93) and using soap for handwashing (OR = 0.61; 95% CI 0.37-0.95) were independently associated with a lower odds of typhoid fever. Poor sanitation facilities appear to be a major source of Salmonella Typhi in Fiji, with transmission by drinking contaminated surface water and consuming unwashed produce. Improved sanitation facilities and protection of surface water sources and produce from contamination by human feces are likely to contribute to typhoid control in Fiji.

Development of a bivalent conjugate vaccine candidate against malaria transmission and typhoid fever.

PubMed

An, So Jung; Scaria, Puthupparampil V; Chen, Beth; Barnafo, Emma; Muratova, Olga; Anderson, Charles; Lambert, Lynn; Chae, Myung Hwa; Yang, Jae Seung; Duffy, Patrick E

2018-05-17

Immune responses to poorly immunogenic antigens, such as polysaccharides, can be enhanced by conjugation to carriers. Our previous studies indicate that conjugation to Vi polysaccharide of Salmonella Typhi may also enhance immunogenicity of some protein carriers. We therefore explored the possibility of generating a bivalent vaccine against Plasmodium falciparum malaria and typhoid fever, which are co-endemic in many parts of the world, by conjugating Vi polysaccharide, an approved antigen in typhoid vaccine, to Pfs25, a malaria transmission blocking vaccine antigen in clinical trials. Vi-Pfs25 conjugates induced strong immune responses against both Vi and Pfs25 in mice, whereas the unconjugated antigens are poorly immunogenic. Functional assays of immune sera revealed potent transmission blocking activity mediated by anti-Pfs25 antibody and serum bactericidal activity due to anti-Vi antibody. Pfs25 conjugation to Vi modified the IgG isotype distribution of antisera, inducing a Th2 polarized immune response against Vi antigen. This conjugate may be further developed as a bivalent vaccine to concurrently target malaria and typhoid fever. Copyright © 2018. Published by Elsevier Ltd.

Environmental Survey of Drinking Water Sources in Kampala, Uganda, during a Typhoid Fever Outbreak

PubMed Central

Kahler, A. M.; Nansubuga, I.; Nanyunja, E. M.; Kaplan, B.; Jothikumar, N.; Routh, J.; Gómez, G. A.; Mintz, E. D.; Hill, V. R.

2017-01-01

ABSTRACT In 2015, a typhoid fever outbreak began in downtown Kampala, Uganda, and spread into adjacent districts. In response, an environmental survey of drinking water source types was conducted in areas of the city with high case numbers. A total of 122 samples was collected from 12 source types and tested for Escherichia coli, free chlorine, and conductivity. An additional 37 grab samples from seven source types and 16 paired large volume (20 liter) samples from wells and springs were also collected and tested for the presence of Salmonella enterica serovar Typhi. Escherichia coli was detected in 60% of kaveras (drinking water sold in plastic bags) and 80% of refilled water bottles; free chlorine was not detected in either source type. Most jerry cans (68%) contained E. coli and had free chlorine residuals below the WHO-recommended level of 0.5 mg/liter during outbreaks. Elevated conductivity readings for kaveras, refilled water bottles, and jerry cans (compared to treated surface water supplied by the water utility) suggested that they likely contained untreated groundwater. All unprotected springs and wells and more than 60% of protected springs contained E. coli. Water samples collected from the water utility were found to have acceptable free chlorine levels and no detectable E. coli. While S. Typhi was not detected in water samples, Salmonella spp. were detected in samples from two unprotected springs, one protected spring, and one refilled water bottle. These data provided clear evidence that unregulated vended water and groundwater represented a risk for typhoid transmission. IMPORTANCE Despite the high incidence of typhoid fever globally, relatively few outbreak investigations incorporate drinking water testing. During waterborne disease outbreaks, measurement of physical-chemical parameters, such as free chlorine residual and electrical conductivity, and of microbiological parameters, such as the presence of E. coli or the implicated etiologic agent, in drinking water samples can identify contaminated sources. This investigation indicated that unregulated vended water and groundwater sources were contaminated and were therefore a risk to consumers during the 2015 typhoid fever outbreak in Kampala. Identification of contaminated drinking water sources and sources that do not contain adequate disinfectant levels can lead to rapid targeted interventions. PMID:28970225

Epidemiological investigation of an outbreak of typhoid fever in Jorhat town of Assam, India.

PubMed

Roy, Jashbeer Singh; Saikia, Lahari; Medhi, Mithu; Tassa, Dipak

2016-10-01

Typhoid fever is a global health problem and is also endemic in India. An outbreak of fever occurred in January 2014 in Jorhat Town in Assam, India. Here we report the results of an investigation done to find out the aetiology and source of the outbreak. The affected areas were visited on January 23, 2014 by a team of Jorhat district Integrated Disease Surveillance Project personnel. A total of 13 blood samples from patients with fever as first symptom and six water samples were collected from the affected areas. The blood samples were cultured and isolates were identified using standard biochemical tests. Isolates were also tested for antimicrobial sensitivity. Widal test was performed on 10 of the 13 blood samples collected. Sanitary survey was carried out to find any leakage in the water supply and also the sewage system of the Jorhat town. Blood culture yielded Salmonella enterica serovar Typhi in six (46.15%) patients whereas Widal test was positive in 10 (76.9%) of 13 patients. Water culture showed presumptive coliform count of >180/100 ml in two out of the six samples tested. Salmonella Typhi was also isolated from water culture of these two samples. Sanitary survey carried out in the affected places showed that the water supply pipes of urban water supply were in close proximity to the sewage drainage system and there were few leakages. The outbreak occurred due to S. Typhi contaminating the water supply. Sanitation and immunization are the two most important components to be stressed to prevent such outbreaks.

Epidemiological investigation of an outbreak of typhoid fever in Jorhat town of Assam, India

PubMed Central

Roy, Jashbeer Singh; Saikia, Lahari; Medhi, Mithu; Tassa, Dipak

2016-01-01

Background & objectives: Typhoid fever is a global health problem and is also endemic in India. An outbreak of fever occurred in January 2014 in Jorhat Town in Assam, India. Here we report the results of an investigation done to find out the aetiology and source of the outbreak. Methods: The affected areas were visited on January 23, 2014 by a team of Jorhat district Integrated Disease Surveillance Project personnel. A total of 13 blood samples from patients with fever as first symptom and six water samples were collected from the affected areas. The blood samples were cultured and isolates were identified using standard biochemical tests. Isolates were also tested for antimicrobial sensitivity. Widal test was performed on 10 of the 13 blood samples collected. Sanitary survey was carried out to find any leakage in the water supply and also the sewage system of the Jorhat town. Results: Blood culture yielded Salmonella enterica serovar Typhi in six (46.15%) patients whereas Widal test was positive in 10 (76.9%) of 13 patients. Water culture showed presumptive coliform count of >180/100 ml in two out of the six samples tested. Salmonella Typhi was also isolated from water culture of these two samples. Sanitary survey carried out in the affected places showed that the water supply pipes of urban water supply were in close proximity to the sewage drainage system and there were few leakages. Interpretation & conclusions: The outbreak occurred due to S. Typhi contaminating the water supply. Sanitation and immunization are the two most important components to be stressed to prevent such outbreaks. PMID:28256469

Knowledge, attitude and practice of hygiene and sanitation in a Burundian refugee camp: implications for control of a Salmonella typhi outbreak

PubMed Central

Nahimana, Marie-Rosette; Ngoc, Candide Tran; Olu, Olushayo; Nyamusore, Jose; Isiaka, Ayodeji; Ndahindwa, Vedaste; Dassanayake, Lakruwan; Rusanganwa, André

2017-01-01

Introduction A Salmonella typhi outbreak was reported in a Burundian refugee camp in Rwanda in October 2015. Transmission persisted despite increased hygiene promotion activities and hand-washing facilities instituted to prevent and control the outbreak. A knowledge, attitude and practice (KAP) study was carried out to assess the effectiveness of ongoing typhoid fever preventive interventions. Methods A cross-sectional survey was conducted in Mahama Refugee Camp of Kirehe District, Rwanda from January to February 2016. Data were obtained through administration of a structured KAP questionnaire. Descriptive, bivariate and multivariate analysis was performed using STATA software. Results A total of 671 respondents comprising 264 (39.3%) males and 407 (60.7%) females were enrolled in the study. A comparison of hand washing practices before and after institution of prevention and control measures showed a 37% increase in the proportion of respondents who washed their hands before eating and after using the toilet (p < 0.001). About 52.8% of participants reported having heard about typhoid fever, however 25.9% had received health education. Only 34.6% and 38.6% of the respondents respectively knew how typhoid fever spreads and is prevented. Most respondents (98.2%) used pit latrines for disposal of feces. Long duration of stay in the camp, age over 35 years and being unemployed were statistically associated with poor hand washing practices. Conclusion The findings of this study underline the need for bolstering up health education and hygiene promotion activities in Mahama and other refugee camp settings. PMID:29184606

Knowledge, attitude and practice of hygiene and sanitation in a Burundian refugee camp: implications for control of a Salmonella typhi outbreak.

PubMed

Nahimana, Marie-Rosette; Ngoc, Candide Tran; Olu, Olushayo; Nyamusore, Jose; Isiaka, Ayodeji; Ndahindwa, Vedaste; Dassanayake, Lakruwan; Rusanganwa, André

2017-01-01

A Salmonella typhi outbreak was reported in a Burundian refugee camp in Rwanda in October 2015. Transmission persisted despite increased hygiene promotion activities and hand-washing facilities instituted to prevent and control the outbreak. A knowledge, attitude and practice (KAP) study was carried out to assess the effectiveness of ongoing typhoid fever preventive interventions. A cross-sectional survey was conducted in Mahama Refugee Camp of Kirehe District, Rwanda from January to February 2016. Data were obtained through administration of a structured KAP questionnaire. Descriptive, bivariate and multivariate analysis was performed using STATA software. A total of 671 respondents comprising 264 (39.3%) males and 407 (60.7%) females were enrolled in the study. A comparison of hand washing practices before and after institution of prevention and control measures showed a 37% increase in the proportion of respondents who washed their hands before eating and after using the toilet (p < 0.001). About 52.8% of participants reported having heard about typhoid fever, however 25.9% had received health education. Only 34.6% and 38.6% of the respondents respectively knew how typhoid fever spreads and is prevented. Most respondents (98.2%) used pit latrines for disposal of feces. Long duration of stay in the camp, age over 35 years and being unemployed were statistically associated with poor hand washing practices. The findings of this study underline the need for bolstering up health education and hygiene promotion activities in Mahama and other refugee camp settings.

Sensitivity and specificity of typhoid fever rapid antibody tests for laboratory diagnosis at two sub-Saharan African sites

PubMed Central

Keddy, Karen H; Sooka, Arvinda; Letsoalo, Maupi E; Hoyland, Greta; Chaignat, Claire Lise; Morrissey, Anne B; Crump, John A

2011-01-01

Abstract Objective To evaluate three commercial typhoid rapid antibody tests for Salmonella Typhi antibodies in patients suspected of having typhoid fever in Mpumalanga, South Africa, and Moshi, United Republic of Tanzania. Methods The diagnostic accuracy of Cromotest® (semiquantitative slide agglutination and single tube Widal test), TUBEX® and Typhidot® was assessed against that of blood culture. Performance was modelled for scenarios with pretest probabilities of 5% and 50%. Findings In total 92 patients enrolled: 53 (57.6%) from South Africa and 39 (42.4%) from the United Republic of Tanzania. Salmonella Typhi was isolated from the blood of 28 (30.4%) patients. The semiquantitative slide agglutination and single-tube Widal tests had positive predictive values (PPVs) of 25.0% (95% confidence interval, CI: 0.6–80.6) and 20.0% (95% CI: 2.5–55.6), respectively. The newer typhoid rapid antibody tests had comparable PPVs: TUBEX®, 54.1% (95% CI: 36.9–70.5); Typhidot® IgM, 56.7% (95% CI: 37.4–74.5); and Typhidot® IgG, 54.3% (95% CI: 36.6–71.2). For a pretest probability of 5%, PPVs were: TUBEX®, 11.0% (95% CI: 6.6–17.9); Typhidot® IgM, 9.1% (95% CI: 5.8–14.0); and Typhidot® IgG, 11.0% (6.3–18.4). For a pretest probability of 50%, PPVs were: TUBEX®, 70.2% (95% CI: 57.3–80.5); Typhidot® IgM, 65.6% (95% CI: 54.0–75.6); and Typhidot® IgG, 70.0% (95% CI: 56.0–81.1). Conclusion Semiquantitative slide agglutination and single-tube Widal tests performed poorly. TUBEX® and Typhidot® may be suitable when pretest probability is high and blood cultures are unavailable, but their performance does not justify deployment in routine care settings in sub-Saharan Africa. PMID:21897484

Indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) and IgM capture ELISA for detection of antibodies to lipopolysaccharide in adult typhoid fever patients in Pakistan.

PubMed

Sippel, J; Bukhtiari, N; Awan, M B; Krieg, R; Duncan, J F; Karamat, K A; Malik, I A; Igbal, L M; Legters, L

1989-06-01

Sera from 339 adult febrile patients in Pakistan were tested for antibodies to Salmonella typhi lipopolysaccharide by indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assay (ELISA) and IgM capture ELISA. A total of 55 patients had S. typhi cultured from their blood, 20 had S. typhi cultured from their stool, 24 were blood or stool culture positive for S. paratyphi A, 41 were culture negative but clinically diagnosed as having enteric fever, 41 had gastrointestinal or urinary tract infections, 41 were clinically diagnosed as having malaria, 20 were smear-positive patients with malaria, 58 had respiratory infections, and the remaining 39 individuals were placed in a miscellaneous group who did not have Salmonella infection. The sensitivities of the indirect IgG ELISA, indirect IgM ELISA, and IgM capture ELISA determined with specimens obtained from the blood culture-positive patients with typhoid fever (positive controls) were 80, 64, and 62%, respectively. The specificities of the assays determined with sera from the patients with respiratory infections (negative controls) were 95, 95, and 97%, respectively. The percentage of smear-positive patients with malaria who were positive by these assays was lower than that in the negative control group. The percentages of individuals in the other patient categories who were positive by these tests were between those obtained with the positive and negative controls. Of the positive controls, 26 were positive by both IgM assays, 9 were IgM positive only by indirect ELISA, and 8 were IgM positive only by IgM capture ELISA. A total of 70% of the positive control patients who were tested for O agglutinins by the Widal tube agglutination assay were positive; however, 29% of the negative control patients were also positive. The indirect IgG ELISA was the single most effective test for the serodiagnosis of typhoid fever in this population.

Indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) and IgM capture ELISA for detection of antibodies to lipopolysaccharide in adult typhoid fever patients in Pakistan.

PubMed Central

Sippel, J; Bukhtiari, N; Awan, M B; Krieg, R; Duncan, J F; Karamat, K A; Malik, I A; Igbal, L M; Legters, L

1989-01-01

Sera from 339 adult febrile patients in Pakistan were tested for antibodies to Salmonella typhi lipopolysaccharide by indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assay (ELISA) and IgM capture ELISA. A total of 55 patients had S. typhi cultured from their blood, 20 had S. typhi cultured from their stool, 24 were blood or stool culture positive for S. paratyphi A, 41 were culture negative but clinically diagnosed as having enteric fever, 41 had gastrointestinal or urinary tract infections, 41 were clinically diagnosed as having malaria, 20 were smear-positive patients with malaria, 58 had respiratory infections, and the remaining 39 individuals were placed in a miscellaneous group who did not have Salmonella infection. The sensitivities of the indirect IgG ELISA, indirect IgM ELISA, and IgM capture ELISA determined with specimens obtained from the blood culture-positive patients with typhoid fever (positive controls) were 80, 64, and 62%, respectively. The specificities of the assays determined with sera from the patients with respiratory infections (negative controls) were 95, 95, and 97%, respectively. The percentage of smear-positive patients with malaria who were positive by these assays was lower than that in the negative control group. The percentages of individuals in the other patient categories who were positive by these tests were between those obtained with the positive and negative controls. Of the positive controls, 26 were positive by both IgM assays, 9 were IgM positive only by indirect ELISA, and 8 were IgM positive only by IgM capture ELISA. A total of 70% of the positive control patients who were tested for O agglutinins by the Widal tube agglutination assay were positive; however, 29% of the negative control patients were also positive. The indirect IgG ELISA was the single most effective test for the serodiagnosis of typhoid fever in this population. PMID:2754002

Evaluation of the antibacterial activity of selected Pakistani honeys against multi-drug resistant Salmonella typhi.

PubMed

Hussain, Muhammad Barkaat; Hannan, Abdul; Akhtar, Naeem; Fayyaz, Ghulam Qadir; Imran, Muhammad; Saleem, Sidrah; Qureshi, Imtiaz Ahmed

2015-02-26

The development of resistance to conventional anti-typhoid drugs and the recent emergence of fluoroquinolone resistance have made it very difficult and expensive to treat typhoid fever. As the therapeutic strategies become even more limited, it is imperative to investigate non-conventional modalities. In this context, honey is a potential candidate for combating antimicrobial resistance because it contains a broad repertoire of antibacterial compounds which act synergistically at multiple sites, thus making it less likely that the bacteria will become resistant. The in vitro antibacterial activity of 100 unifloral honey samples against a blood culture isolate of multi-drug resistant (MDR) Salmonella typhi were investigated. All honey samples were evaluated for both total (acidity, osmolarity, hydrogen peroxide and non-peroxide activity) and plant derived non-peroxide antibacterial activity by agar well diffusion assay at 50% and 25% dilution in sterile distilled water and 25% in catalase solution. Manuka (Unique Manuka Factor-21) honey was used for comparison. The phenol equivalence of each honey sample from 2% to 7% (w/v) phenol was obtained from regression analysis. The antibacterial potential of each honey sample was expressed as its equivalent phenol concentration. The honey samples which showed antibacterial activity equivalent to or greater than manuka honey were considered therapeutically active honeys. Nineteen honey samples (19%) displayed higher hydrogen peroxide related antibacterial activity (16-20% phenol), which is more than that of manuka honey (21-UMF). A total of 30% of the honey samples demonstrated antibacterial activity between 11 and 15% phenol similar to that of manuka honey while 51% of the honey samples did not exhibit any zone of inhibition against MDR-S. typhi at 50% (w/v) dilution. None of the indigenous honey samples displayed non-peroxide antibacterial activity. Only manuka honey showed non-peroxide antibacterial activity at 25% dilution (w/v) in catalase solution. The honey samples which displayed antibacterial activity equal to or greater than manuka honey may be useful in the clinical conditions where higher hydrogen peroxide related antibacterial activity is required. Manuka honey, which is known to possess non-peroxide antibacterial activity, warrants further evaluation in a suitable typhoid animal model.

Development of a Simple, Peripheral-Blood-Based Lateral-Flow Dipstick Assay for Accurate Detection of Patients with Enteric Fever

PubMed Central

Khan, Iqbal Hassan; Sayeed, M. Abu; Sultana, Nishat; Islam, Kamrul; Amin, Jakia; Faruk, M. Omar; Khan, Umama; Khanam, Farhana; Ryan, Edward T.

2016-01-01

Enteric fever is a systemic infection caused by typhoidal strains of Salmonella enterica and is a significant cause of mortality and morbidity in many parts of the world, especially in resource-limited areas. Unfortunately, currently available diagnostic tests for enteric fever lack sensitivity and/or specificity. No true clinically practical gold standard for diagnosing patients with enteric fever exists. Unfortunately, microbiologic culturing of blood is only 30 to 70% sensitive although 100% specific. Here, we report the development of a lateral-flow immunochromatographic dipstick assay based on the detection of Salmonella enterica serovar Typhi (S. Typhi) lipopolysaccharide (LPS)-specific IgG in lymphocyte culture secretion. We tested the assay using samples from 142 clinically suspected enteric fever patients, 28 healthy individuals residing in a zone where enteric fever is endemic, and 35 patients with other febrile illnesses. In our analysis, the dipstick detected all blood culture-confirmed S. Typhi cases (48/48) and 5 of 6 Salmonella enterica serovar Paratyphi A blood cultured-confirmed cases. The test was negative in all 35 individuals febrile with other illnesses and all 28 healthy controls from the zone of endemicity. The test was positive in 19 of 88 individuals with suspected enteric fever but with negative blood cultures. Thus, the dipstick had a sensitivity of 98% compared to blood culture results and a specificity that ranged from 78 to 100% (95% confidence interval [CI], 70 to 100%), depending on the definition of a true negative. These results suggest that this dipstick assay can be very useful for the detection of enteric fever patients especially in regions of endemicity. PMID:26961857

Investigation of a community outbreak of typhoid fever associated with drinking water

PubMed Central

2009-01-01

Background This report is about the investigation of an outbreak of typhoid fever claimed three human lives and left more than 300 people suffered within one week. The aim of this report is to draw the attention of global health community towards the areas that are still far from basic human essentialities. Methods A total of 250 suspected cases of typhoid fever were interviewed, out of which 100 were selected for sample collection on the basis of criteria included temperature > 38°C since the onset of outbreak, abdominal discomfort, diarrhea, vomiting and weakness. Food and water samples were also collected and analyzed microbiologically. Results Inhabitants of village lived in poor and unhygienic conditions with no proper water supply or sewage disposal facilities and other basic necessities of life. They consumed water from a nearby well which was the only available source of drinking water. Epidemiological evidences revealed the gross contamination of well with dead and decaying animal bodies, their fecal material and garbage. Microbiological analysis of household and well water samples revealed the presence of heavy bacterial load with an average total aerobic count 106-109 CFU/ml. A number of Gram positive and Gram negative bacteria including Escherichia coli, Klebsiella, Bacillus species, Staphylococcus species, Enterobacter species, and Pseudomonas aeruginosa were isolated. Lab investigations confirmed the presence of multidrug resistant strain of Salmonella enterica serovar Typhi in 100% well water, 65% household water samples and 2% food items. 22% of clinical stool samples were tested positive with Salmonella enterica serover Typhi Conclusions This study indicated the possible involvement of well water in outbreaks. In order to avoid such outbreaks in future, we contacted the local health authorities and urged them to immediately make arrangements for safe drinking water supply. PMID:20021691

Inhibition of Salmonella typhi growth using extremely low frequency electromagnetic (ELF-EM) waves at resonance frequency.

PubMed

Fadel, M A; Mohamed, S A; Abdelbacki, A M; El-Sharkawy, A H

2014-08-01

Typhoid is a serious disease difficult to be treated with conventional drugs. The aim of this study was to demonstrate a new method for the control of Salmonella typhi growth, through the interference with the bioelectric signals generated from the microbe during cell division by extremely low frequency electromagnetic waves (ELF-EMW-ELF-EM) at resonance frequency. Isolated Salmonella typhi was subjected to square amplitude modulated waves (QAMW) with different modulation frequencies from two generators with constant carrier frequency of 10 MHz, amplitude of 10 Vpp, modulating depth ± 2 Vpp and constant field strength of 200 V m(-1) at 37°C. Both the control and exposed samples were incubated at the same conditions during the experiment. The results showed that there was highly significant inhibition effect for Salm. typhi exposed to 0·8 Hz QAMW for a single exposure for 75 min. Dielectric relaxation, TEM and DNA results indicated highly significant changes in the molecular structure of the DNA and cellular membrane resulting from the exposure to the inhibiting EM waves. It was concluded that finding out the inhibiting resonance frequency of ELF-EM waves that deteriorates Salm. typhi growth will be promising method for the treatment of Salm. typhi infection either in vivo or in vitro. This new non-invasive technique for treatment of bacterial infections is of considerable interest for the use in medical and biotechnological applications. © 2014 The Society for Applied Microbiology.

Antimicrobial Drug Resistance of Salmonella enterica Serovar Typhi in Asia and Molecular Mechanism of Reduced Susceptibility to the Fluoroquinolones▿

PubMed Central

Chau, Tran Thuy; Campbell, James Ian; Galindo, Claudia M.; Van Minh Hoang, Nguyen; Diep, To Song; Nga, Tran Thu Thi; Van Vinh Chau, Nguyen; Tuan, Phung Quoc; Page, Anne Laure; Ochiai, R. Leon; Schultsz, Constance; Wain, John; Bhutta, Zulfiqar A.; Parry, Christopher M.; Bhattacharya, Sujit K.; Dutta, Shanta; Agtini, Magdarina; Dong, Baiqing; Honghui, Yang; Anh, Dang Duc; Canh, Do Gia; Naheed, Aliya; Albert, M. John; Phetsouvanh, Rattanaphone; Newton, Paul N.; Basnyat, Buddha; Arjyal, Amit; La, Tran Thi Phi; Rang, Nguyen Ngoc; Phuong, Le Thi; Van Be Bay, Phan; von Seidlein, Lorenz; Dougan, Gordon; Clemens, John D.; Vinh, Ha; Hien, Tran Tinh; Chinh, Nguyen Tran; Acosta, Camilo J.; Farrar, Jeremy; Dolecek, Christiane

2007-01-01

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83→Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions. PMID:17908946

Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

PubMed Central

Sjölund-Karlsson, Maria; Gordon, Melita A.; Parry, Christopher M.

2015-01-01

SUMMARY Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015. PMID:26180063

Functional Activity of Antibodies Directed towards Flagellin Proteins of Non-Typhoidal Salmonella

PubMed Central

Boyd, Mary A.; Wang, Jin Y.; Tulapurkar, Mohan E.; Pasetti, Marcela F.; Levine, Myron M.; Simon, Raphael

2016-01-01

Non-typhoidal Salmonella (NTS) serovars Typhimurium and Enteritidis are major causes of invasive bacterial infections in children under 5 years old in sub-Saharan Africa, with case fatality rates of ~20%. There are no licensed NTS vaccines for humans. Vaccines that induce antibodies against a Salmonella Typhi surface antigen, Vi polysaccharide, significantly protect humans against typhoid fever, establishing that immune responses to Salmonella surface antigens can be protective. Flagella proteins, abundant surface antigens in Salmonella serovars that cause human disease, are also powerful immunogens, but the functional capacity of elicited anti-flagellar antibodies and their role in facilitating bacterial clearance has been unclear. We examined the ability of anti-flagellar antibodies to mediate microbial killing by immune system components in-vitro and assessed their role in protecting mice against invasive Salmonella infection. Polyclonal (hyperimmune sera) and monoclonal antibodies raised against phase 1 flagellin proteins of S. Enteritidis and S. Typhimurium facilitated bacterial uptake and killing of the homologous serovar pathogen by phagocytes. Polyclonal anti-flagellar antibodies accompanied by complement also achieved direct bacterial killing. Serum bactericidal activity was restricted to Salmonella serovars expressing the same flagellin used as immunogen. Notably, individual anti-flagellin monoclonal antibodies with complement were not bactericidal, but this biological activity was restored when different monoclonal anti-flagellin antibodies were combined. Passive transfer immunization with a monoclonal IgG antibody specific for phase 1 flagellin from S. Typhimurium protected mice against lethal challenge with a representative African invasive S. Typhimurium strain. These findings have relevance for the use of flagellin proteins in NTS vaccines, and confirm the role of anti-flagellin antibodies as mediators of protective immunity. PMID:26998925

Environmental Survey of Drinking Water Sources in Kampala, Uganda, during a Typhoid Fever Outbreak.

PubMed

Murphy, J L; Kahler, A M; Nansubuga, I; Nanyunja, E M; Kaplan, B; Jothikumar, N; Routh, J; Gómez, G A; Mintz, E D; Hill, V R

2017-12-01

In 2015, a typhoid fever outbreak began in downtown Kampala, Uganda, and spread into adjacent districts. In response, an environmental survey of drinking water source types was conducted in areas of the city with high case numbers. A total of 122 samples was collected from 12 source types and tested for Escherichia coli , free chlorine, and conductivity. An additional 37 grab samples from seven source types and 16 paired large volume (20 liter) samples from wells and springs were also collected and tested for the presence of Salmonella enterica serovar Typhi. Escherichia coli was detected in 60% of kaveras (drinking water sold in plastic bags) and 80% of refilled water bottles; free chlorine was not detected in either source type. Most jerry cans (68%) contained E. coli and had free chlorine residuals below the WHO-recommended level of 0.5 mg/liter during outbreaks. Elevated conductivity readings for kaveras, refilled water bottles, and jerry cans (compared to treated surface water supplied by the water utility) suggested that they likely contained untreated groundwater. All unprotected springs and wells and more than 60% of protected springs contained E. coli Water samples collected from the water utility were found to have acceptable free chlorine levels and no detectable E. coli While S Typhi was not detected in water samples, Salmonella spp. were detected in samples from two unprotected springs, one protected spring, and one refilled water bottle. These data provided clear evidence that unregulated vended water and groundwater represented a risk for typhoid transmission. IMPORTANCE Despite the high incidence of typhoid fever globally, relatively few outbreak investigations incorporate drinking water testing. During waterborne disease outbreaks, measurement of physical-chemical parameters, such as free chlorine residual and electrical conductivity, and of microbiological parameters, such as the presence of E. coli or the implicated etiologic agent, in drinking water samples can identify contaminated sources. This investigation indicated that unregulated vended water and groundwater sources were contaminated and were therefore a risk to consumers during the 2015 typhoid fever outbreak in Kampala. Identification of contaminated drinking water sources and sources that do not contain adequate disinfectant levels can lead to rapid targeted interventions. Copyright © 2017 American Society for Microbiology.

Global Genomic Analysis of Prostate, Breast and Pancreatic Cancer

DTIC Science & Technology

2012-10-01

fever virus (Lauck et al. 2011). The success of transposon-based genomic library construction for genomic analyses suggests that it should be possible...2011. Novel, divergent simian hemorrhagic Fever viruses in a wild ugandan red colobus Gertz et al. 140 Genome Research www.genome.org Cold Spring...2009. A strand-specific RNA-Seq analysis of the transcriptome of the typhoid bacillus Salmonella typhi. PLoS Genet 5: e1000569. doi: 10.1371

Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a-based prime boost immunization strategy

PubMed Central

Baillie, Leslie W.J.; Rodriguez, Ana L.; Moore, Stephen; Atkins, Helen S.; Feng, Chiguang; Nataro, James P.; Pasetti, Marcela F.

2008-01-01

We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [1]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax. PMID:18805452

Association between specific plasmids and relapse in typhoid fever.

PubMed Central

Gotuzzo, E; Morris, J G; Benavente, L; Wood, P K; Levine, O; Black, R E; Levine, M M

1987-01-01

We studied isolates from 73 patients hospitalized with typhoid fever in Lima, Peru. Of these 73 patients, 11 (15%) suffered a clinical relapse, with fever and positive blood cultures, within 3 months of their original illness. Using plasmids as epidemiologic markers, we found that three patients who subsequently relapsed were initially infected with more than one strain of Salmonella typhi. There was a highly significant association between relapse and isolation of a strain containing either a 24- or a 38-kilobase plasmid at the time of the original infection; however, we were unable to show any evidence of homology between these two plasmids. Our data indicate that infection with multiple strains is not uncommon in this endemic area and suggest that relapse may be partly strain dependent. Images PMID:2821064

Structural basis of typhod: Salmonella typhi type IVb pilin (PilS) and cystic fibrosis transmembrane conductance regulator interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balakrishna, A.; Saxena, A; Mok, H

2009-01-01

The type IVb pilus of the enteropathogenic bacteria Salmonella typhi is a major adhesion factor during the entry of this pathogen into gastrointestinal epithelial cells. Its target of adhesion is a stretch of 10 residues from the first extracellular domain of cystic fibrosis transmembrane conductance regulator (CFTR). The crystal structure of the N-terminal 25 amino acid deleted S. typhi native PilS protein (PilS), which makes the pilus, was determined at 1.9 A resolution by the multiwavelength anomalous dispersion method. Also, the structure of the complex of PilS and a target CFTR peptide, determined at 1.8 A, confirms that residues 113-117more » (NKEER) of CFTR are involved in binding with the pilin protein and gives us insight on the amino acids that are essential for binding. Furthermore, we have also explored the role of a conserved disulfide bridge in pilus formation. The subunit structure and assembly architecture are crucial for understanding pilus functions and designing suitable therapeutics against typhoid.« less

Liver function assessment in malaria, typhoid and malaria-typhoid co-infection in Aba, Abia State, Nigeria.

PubMed

Enemchukwu, B N; Ibe, C C; Udedi, S C; Iroha, A; Ubaoji, K I; Ogundapo, S S

2014-06-01

Malaria and typhoid fever are among the most endemic diseases in the tropics and are associated with poverty and underdevelopment with significant morbidity and mortality. Both diseases can lead to liver damage if not properly treated. The liver function assessment was therefore conducted on (90) volunteer patients; comprising (30) patients with malaria only, (30) with typhoid only and (30) with malaria-typhoid co-infection randomly selected from Abia State University Teaching Hospital, Aba, Abia State, Nigeria and (20) healthy individuals were used as control. Blood samples collected from these subjects were screened for malaria parasite and Staphylococcus typhi using standard methods. Mean serum levels of ALP (112.55±84.23), AST (31.33±12.80), ALT (23.10±11.84), TB (19.43±5.02), CB (5.91±3.03) and ALP (116.69±48.68), AST (28.33±11.72), ALT (22.8±5.94), TB (19.31±5.84),CB (5.60±2.50) were obtained for those subjects with malaria and typhoid respectively and subjects with malaria-typhoid co-infection recorded the following; ALP (134.33±56.62), AST (33.97±8.43), ALT (24.40±4.37),TB (21.27±2.96),CB (6.58±3.10) while the control subjects had mean serum levels ofALP (71.05±18.18), AST (16.65±7.45), ALT (13.85±6.09), TB (10.05±4.85) and CB (3.00±1.67). These mean values were subjected to a statistical test using students t-test which revealed a significant increase (p<0.05).The results suggest that malaria, typhoid and malaria-typhoid co-infection can elevate ALP, AST, ALT, TB and CB serum levels and can lead to liver damage if not properly treated.

Molecular typing and resistance analysis of travel-associated Salmonella enterica serotype Typhi.

PubMed

Tatavarthy, A; Sanderson, R; Peak, K; Scilabro, G; Davenhill, P; Cannons, A; Amuso, P

2012-08-01

Salmonella enterica serotype Typhi is a human pathogen causing 12 to 30% mortality and requiring antibiotic therapy to control the severity of the infection. Typhoid fever in United States is often associated with foreign travel to areas of endemicity. Increasing resistance to multiple drugs, including quinolones, is associated with decreased susceptibility to ciprofloxacin (DCS). We investigated 31 clinical strains isolated in Florida from 2007 to 2010, associated with travel to six countries, to examine the clonal distribution of the organism and apparent nalidixic acid (NAL) resistance. The strains were isolated from blood or stool of patients aged 2 to 68 years. The isolates were subtyped by ribotyping and pulsed-field gel electrophoresis. Susceptibilities to 15 antimicrobials were determined, and the isolates were screened for integrons and gyrase A gene mutations. Both typing techniques effectively segregated the strains. Identical clones were associated with different countries, while diverse types coexisted in the same geographic location. Fifty-one percent of the strains were resistant to at least one antimicrobial, and five were resistant to three or more drugs (multidrug resistant [MDR]). All 12 isolates from the Indian subcontinent were resistant to at least one drug, and 83% of those were resistant to NAL. Three of the MDR strains harbored a 750-bp integron containing the dfr7 gene. Ninety-three percent of the resistant strains showed a DCS profile. All the NAL-resistant strains contained point mutations in the quinolone resistance-determining region of gyrA. This study affirms the global clonal distribution, concomitant genetic heterogeneity, and increased NAL resistance of S. enterica serovar Typhi.

Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006–2009

PubMed Central

Tabu, Collins; Breiman, Robert F.; Ochieng, Benjamin; Aura, Barrack; Cosmas, Leonard; Audi, Allan; Olack, Beatrice; Bigogo, Godfrey; Ongus, Juliette R.; Fields, Patricia; Mintz, Eric; Burton, Deron; Oundo, Joe; Feikin, Daniel R.

2012-01-01

Background The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change. Methods As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006–2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured. Results NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy. Conclusions NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa. PMID:22363591

Small-Scale Terrorist Attacks Using Chemical and Biological Agents: An Assessment Framework and Preliminary Comparisons

DTIC Science & Technology

2004-06-23

Vibrio cholerae ) + — — — + Unknown Salmonella Typhimurium + — + — — Unknown Typhoid fever (Salmonella Typhi) + O — — — Unknown Source: This...disseminated by contamination of food or drink. Cholera bb ( Vibrio cholerae ) Cholera occurs in many of the developing countries of Africa and Asia...diseaseinfo/cholera_g.htm]; the Health Canada Material Safety Data Sheet - Infectious Substances for Vibrio cholerae , found online at [http://www.hc-sc.gc.ca

Crystal structure of an antigenic outer-membrane protein from Salmonella Typhi suggests a potential antigenic loop and an efflux mechanism.

PubMed

Guan, Hong-Hsiang; Yoshimura, Masato; Chuankhayan, Phimonphan; Lin, Chien-Chih; Chen, Nai-Chi; Yang, Ming-Chi; Ismail, Asma; Fun, Hoong-Kun; Chen, Chun-Jung

2015-11-13

ST50, an outer-membrane component of the multi-drug efflux system from Salmonella enterica serovar Typhi, is an obligatory diagnostic antigen for typhoid fever. ST50 is an excellent and unique diagnostic antigen with 95% specificity and 90% sensitivity and is used in the commercial diagnosis test kit (TYPHIDOT(TM)). The crystal structure of ST50 at a resolution of 2.98 Å reveals a trimer that forms an α-helical tunnel and a β-barrel transmembrane channel traversing the periplasmic space and outer membrane. Structural investigations suggest significant conformational variations in the extracellular loop regions, especially extracellular loop 2. This is the location of the most plausible antibody-binding domain that could be used to target the design of new antigenic epitopes for the development of better diagnostics or drugs for the treatment of typhoid fever. A molecule of the detergent n-octyl-β-D-glucoside is observed in the D-cage, which comprises three sets of Asp361 and Asp371 residues at the periplasmic entrance. These structural insights suggest a possible substrate transport mechanism in which the substrate first binds at the periplasmic entrance of ST50 and subsequently, via iris-like structural movements to open the periplasmic end, penetrates the periplasmic domain for efflux pumping of molecules, including poisonous metabolites or xenobiotics, for excretion outside the pathogen.

Typhoid fever outbreak associated with frozen mamey pulp imported from Guatemala to the western United States, 2010.

PubMed

Loharikar, Anagha; Newton, Anna; Rowley, Patricia; Wheeler, Charlotte; Bruno, Tami; Barillas, Haroldo; Pruckler, James; Theobald, Lisa; Lance, Susan; Brown, Jeffrey M; Barzilay, Ezra J; Arvelo, Wences; Mintz, Eric; Fagan, Ryan

2012-07-01

Fifty-four outbreaks of domestically acquired typhoid fever were reported between 1960 and 1999. In 2010, the Southern Nevada Health District detected an outbreak of typhoid fever among persons who had not recently travelled abroad. We conducted a case-control study to examine the relationship between illness and exposures. A case was defined as illness with the outbreak strain of Salmonella serotype Typhi, as determined by pulsed-field gel electrophoresis (PFGE), with onset during 2010. Controls were matched by neighborhood, age, and sex. Bivariate and multivariate statistical analyses were completed using logistic regression. Traceback investigation was completed. We identified 12 cases in 3 states with onset from 15 April 2010 to 4 September 2010. The median age of case patients was 18 years (range, 4-48 years), 8 (67%) were female, and 11 (92%) were Hispanic. Nine (82%) were hospitalized; none died. Consumption of frozen mamey pulp in a fruit shake was reported by 6 of 8 case patients (75%) and none of the 33 controls (matched odds ratio, 33.9; 95% confidence interval, 4.9). Traceback investigations implicated 2 brands of frozen mamey pulp from a single manufacturer in Guatemala, which was also implicated in a 1998-1999 outbreak of typhoid fever in Florida. Reporting of individual cases of typhoid fever and subtyping of isolates by PFGE resulted in rapid detection of an outbreak associated with a ready-to-eat frozen food imported from a typhoid-endemic region. Improvements in food manufacturing practices and monitoring will prevent additional outbreaks.

Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever

PubMed Central

Blohmke, Christoph J.; Hill, Jennifer; Darton, Thomas C.; Carvalho-Burger, Matheus; Eustace, Andrew; Jones, Claire; Schreiber, Fernanda; Goodier, Martin R.; Dougan, Gordon; Nakaya, Helder I.; Pollard, Andrew J.

2017-01-01

The mechanisms by which oral, live-attenuated vaccines protect against typhoid fever are poorly understood. Here, we analyze transcriptional responses after vaccination with Ty21a or vaccine candidate, M01ZH09. Alterations in response profiles were related to vaccine-induced immune responses and subsequent outcome after wild-type Salmonella Typhi challenge. Despite broad genetic similarity, we detected differences in transcriptional responses to each vaccine. Seven days after M01ZH09 vaccination, marked cell cycle activation was identified and associated with humoral immunogenicity. By contrast, vaccination with Ty21a was associated with NK cell activity and validated in peripheral blood mononuclear cell stimulation assays confirming superior induction of an NK cell response. Moreover, transcriptional signatures of amino acid metabolism in Ty21a recipients were associated with protection against infection, including increased incubation time and decreased severity. Our data provide detailed insight into molecular immune responses to typhoid vaccines, which could aid the rational design of improved oral, live-attenuated vaccines against enteric pathogens. PMID:29075261

Peptide mimotopes of complex carbohydrates in Salmonella enterica serovar typhi which react with both carbohydrate-specific monoclonal antibody and polyclonal sera from typhoid patients.

PubMed

Thong, Kwai-Lin; Tang, Swee-Seong; Tan, Wen-Siang; Devi, Shamala

2007-01-01

Polyclonal sera from typhoid patients and a monoclonal antibody, mAb ATVi, which recognizes the capsular polysaccharide Vi antigen (ViCPS), were used to select for peptides that mimic the ViCPS by using a phage-displayed random 12-mer peptide library. Two major common mimotopes selected from the library carried the amino acid sequences TSHHDSHGLHRV and ENHSPVNIAHKL. Enzyme-linked immunosorbent assays (ELISAs) showed that these peptides carry mimotopes to ViCPS. Phage clones that contained the 12-mer peptides were also tested against pooled/individual typhoid patients' sera and found to have 3 to 5 times higher binding compared to normal sera. By using Phage-ELISA assays, the derived synthetic peptides, TSHHDSHGLHRV and ENHSPVNIAHKL, were tested against a monoclonal antibody mAb ATVi and over 2-fold difference in binding was found between these peptides and a control unrelated peptide, CTLTTKLYC. Inhibition of the mAb's binding to ViCPS indicated that the synthetic peptides successfully competed with the capsular polysaccharide for antibody binding.

Typhoid fever: A report on a point-source outbreak of 69 cases in Cape Town.

PubMed

Popkiss, M E

1980-03-01

In 1978, after a party in a Cape Town suburb attended by several hundred people, 69 persons were treated for typhoid fever. The precise source of the infection could not be traced, although it is reasonable to suppose that food eaten at the party had been contaminated by the main caterer. All 57 cultures of Salmonella typhi phage-typed were of phage type 46, including that obtained from the stool of the main caterer, who was asymptomatic. An epidemiological profile of the cases and an account of the management of the outbreak is given. There were no deaths and no patient became a carrier. Although the outbreak was contained, certain problems relating thereto are aired, including in particular the potential hazard of food-borne disease wherever housing and environmental standards are low.

Vaccination of active component US military personnel against Salmonella Typhi.

PubMed

Porter, Chad K; Sorrell, Tia; Mitra, Indrani; Riddle, Mark S

2017-03-27

Vaccination against Salmonella Typhi is one of the leading public health interventions reducing the risk of typhoid fever. There are two available licensed vaccines, Vivotif, oral live-attenuated, and Typhim Vi, intramuscular Vi capsular polysaccharide. The US military is a high risk travel population commonly vaccinated for S. Typhi. We describe the use of S. Typhi vaccination in this population and the acute reactogenicity profile of these vaccines. Data were obtained from the Defense Medical Surveillance System and vaccination identified between 1998 and 2011 from vaccination codes. Clinical outcomes were assessed for four weeks post vaccination. Adverse event rates and odds ratios were estimated across the two vaccine types. A total of 1.9million predominately male military personnel received 3.6 million S. Typhi vaccinations with 94.3% of vaccinees receiving the Vi capsule vaccine though variability in the vaccine administered was observed. Receipt of other vaccinations in the 6months surrounding the S. Typhi vaccine was common. Rates of nausea (195 per 100,000 vaccinations), headache (13 per 100,000 vaccinations) and fever (40 per 100,000 vaccinations) were significantly higher following Vi capsule vaccination compared to receipt of Vivotif (130, 2, 10 per 100,000 vaccinations, respectively). In contrast the rates of rash and non-infectious diarrhea (186 and 426 per 100,000 vaccinations, respectively) were increased in those receiving Vivotif compared to the Vi capsule vaccine. The US military is a major consumer of S. Typhi vaccines. The parenterally administered vaccine appears to be more amenable, though we were limited in our ability to assess the reasons for its higher usage. While we observed a higher rate of several adverse events in subjects receiving the intramuscular vaccination, the overall rate of these events was low. Future studies assessing more long-term health outcomes are warranted. Published by Elsevier Ltd.

An Unmutated IgM Response to the Vi Polysaccharide of Salmonella Typhi Contributes to Protective Immunity in a Murine Model of Typhoid.

PubMed

Pandya, Kalgi D; Palomo-Caturla, Isabel; Walker, Justin A; K Sandilya, Vijay; Zhong, Zhijiu; Alugupalli, Kishore R

2018-06-15

T cell-dependent B cell responses typically develop in germinal centers. Abs generated during such responses are isotype switched and have a high affinity to the Ag because of somatic hypermutation of Ab genes. B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice. To test the extent to which unmutated polysaccharide-specific IgM confers protective immunity, we immunized wildtype and AID -/- mice with either heat-killed Salmonella enterica serovar Typhi ( S. Typhi) or purified Vi polysaccharide (ViPS). We found that wildtype and AID -/- mice immunized with heat-killed S. Typhi generated similar anti-ViPS IgM responses. As expected, wildtype, but not AID -/- mice generated ViPS-specific IgG. However, the differences in the Ab-dependent killing of S. Typhi mediated by the classical pathway of complement activation were not statistically significant. In ViPS-immunized wildtype and AID -/- mice, the ViPS-specific IgM levels and S. Typhi bactericidal Ab titers at 7 but not at 28 d postimmunization were also comparable. To test the protective immunity conferred by these immunizations, mice were challenged with a chimeric S. Typhimurium strain expressing ViPS. Compared with their naive counterparts, immunized wildtype and AID -/- mice exhibited significantly reduced bacterial burden regardless of the route of infection. These data indicate that an unmutated IgM response to ViPS contributes to protective immunity to S. Typhi. Copyright © 2018 by The American Association of Immunologists, Inc.

Non-crosslinking gold nanoprobe-LAMP for simple, colorimetric, and specific detection of Salmonella typhi

NASA Astrophysics Data System (ADS)

Bozorgmehr, Ali; Yazdanparast, Razieh; Mollasalehi, Hamidreza

2016-12-01

In this study, we developed a non-crosslinking gold nanoprobe loop-mediated isothermal amplification (LAMP) method for nanodiagnosis of bacterial typhoid fever source, Salmonella typhi. Therefore, a unique region in the S. typhi genomic DNA was targeted for LAMP amplification using a specific set of four precisely designed primers. Also, for specific colorimetric visualization of the amplicons, a thiolated oligonucleotide probe, complementary to the single-stranded loop region of the amplicons between F2 and F1C segments, was designed. The probe was bound to the surface of gold nanoparticles via covalent bonds. Increasing the salt concentration in the detection reaction medium led to aggregation of nanoprobes in the blank and the negative vessels in a time-dependent form. That was followed by a change in the surface plasmon resonance (SPR) leading to blue/black color that was observable by the naked eyes after about 5 min. Meanwhile, the original pink/red color was retained in the positive sample due to the large interparticle spaces and the stability against the ionic strength elevation which persisted for about 30 min. The whole process of DNA extraction, amplification, and detection took less than 2 h with a sensitivity of 20 CFU/ml. The developed gold nanoprobe-LAMP could serve as a simple, rapid, and cost-effective method for nanodiagnosis of S. typhi in point-of-need applications.

Small-Scale Terrorist Attacks Using Chemical and Biological Agents: An Assessment Framework and Preliminary Comparisons

DTIC Science & Technology

2004-05-20

Unknown Cholera ( Vibrio cholerae ) + — — — + Unknown Salmonella Typhimurium + — + — — Unknown Typhoid fever (Salmonella Typhi) + O — — — Unknown... Cholera bb ( Vibrio cholerae ) Cholera occurs in many of the developing countries of Africa and Asia, especially where sanitary conditions are not optimal...Safety Data Sheet - Infectious Substances for Vibrio cholerae , found online at [http://www.hc-sc.gc.ca/pphb-dgspsp/msds-ftss/msds164e.html]; D. Hank

Evaluation of an electricity-free, culture-based approach for detecting typhoidal Salmonella bacteremia during enteric fever in a high burden, resource-limited setting.

PubMed

Andrews, Jason R; Prajapati, Krishna G; Eypper, Elizabeth; Shrestha, Poojan; Shakya, Mila; Pathak, Kamal R; Joshi, Niva; Tiwari, Priyanka; Risal, Manisha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Wen, Shawn; Smith, Amy B; Maru, Duncan; Basnyat, Buddha; Baker, Stephen; Farrar, Jeremy; Ryan, Edward T; Hohmann, Elizabeth; Arjyal, Amit

2013-01-01

In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%-98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.

Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

DOE PAGES

Kintz, Erica; Heiss, Christian; Black, Ian; ...

2017-02-06

Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains weremore » engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.« less

Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kintz, Erica; Heiss, Christian; Black, Ian

Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains weremore » engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.« less

Epidemiological Characteristics and Clinical Treatment Outcome of Typhoid Fever in Ningbo, China, 2005-2014: Pulsed-Field Gel Electorophoresis Results Revealing Great Proportion of Common Transmission Sources.

PubMed

Song, Qifa; Yang, Yuanbin; Lin, Wenping; Yi, Bo; Xu, Guozhang

2017-09-25

We aimed to describe the molecular epidemiological characteristics and clinical treatment outcome of typhoid fever in Ningbo, China during 2005-2014. Eighty-eight Salmonella Typhi isolates were obtained from 307 hospitalized patients. Three prevalent pulsed-field gel electrophoresis (PFGE) patterns of 54 isolates from 3 outbreaks were identified. Overall, there were 64 (72.7%) isolates from clustered cases and 24 (27.3%) isolates from sporadic cases. Resistance to nalidixic acid (NAL) (n = 47; 53.4%) and ampicillin (AMP) (n = 40; 45.4%) and rare resistance to tetracycline (TET) (n = 2; 2.3%) and gentamicin (GEN) (n = 2; 2.3%) were observed. No isolates resistant to cefotaxime (CTX), chloramphenicol (CL), ciprofloxacin (CIP), and trimethoprim-sulfamethoxazole (SXT) were found. The occurrence of reduced sensitivity to CIP was 52.3% (n = 46). The medians of fever clearance time in cases with and without complications were 7 (interquartile range (IQR): 4-10) and 5 (IQR: 3-7) days (P = 0.001), respectively, when patients were treated with CIP or levofloxacin (LEV) and/or third-generation cephalosporins (CEP). Rates of serious complications were at low levels: peritonitis (2.3%), intestinal hemorrhage (6.8%), and intestinal perforation (1.1%). The present study revealed a long-term clustering trend with respect to PFGE patterns, occasional outbreaks, and the rapid spread of AMP resistance and decreased CIP susceptibility among S. Typhi isolates in recent years.

Health at the Sub-catchment Scale: Typhoid and Its Environmental Determinants in Central Division, Fiji.

PubMed

Jenkins, Aaron Peter; Jupiter, Stacy; Mueller, Ute; Jenney, Adam; Vosaki, Gandercillar; Rosa, Varanisese; Naucukidi, Alanieta; Mulholland, Kim; Strugnell, Richard; Kama, Mike; Horwitz, Pierre

2016-12-01

The impact of environmental change on transmission patterns of waterborne enteric diseases is a major public health concern. This study concerns the burden and spatial nature of enteric fever, attributable to Salmonella Typhi infection in the Central Division, Republic of Fiji at a sub-catchment scale over 30-months (2013-2015). Quantitative spatial analysis suggested relationships between environmental conditions of sub-catchments and incidence and recurrence of typhoid fever. Average incidence per inhabited sub-catchment for the Central Division was high at 205.9/100,000, with cases recurring in each calendar year in 26% of sub-catchments. Although the numbers of cases were highest within dense, urban coastal sub-catchments, the incidence was highest in low-density mountainous rural areas. Significant environmental determinants at this scale suggest increased risk of exposure where sediment yields increase following runoff. The study suggests that populations living on large systems that broaden into meandering mid-reaches and floodplains with alluvial deposition are at a greater risk compared to small populations living near small, erosional, high-energy headwaters and small streams unconnected to large hydrological networks. This study suggests that anthropogenic alteration of land cover and hydrology (particularly via fragmentation of riparian forest and connectivity between road and river networks) facilitates increased transmission of typhoid fever and that environmental transmission of typhoid fever is important in Fiji.

Repression of Salmonella enterica phoP Expression by Small Molecules from Physiological Bile

PubMed Central

Antunes, L. Caetano M.; Wang, Melody; Andersen, Sarah K.; Ferreira, Rosana B. R.; Kappelhoff, Reinhild; Han, Jun; Borchers, Christoph H.

2012-01-01

Infection with Salmonella enterica serovar Typhi in humans causes the life-threatening disease typhoid fever. In the laboratory, typhoid fever can be modeled through the inoculation of susceptible mice with Salmonella enterica serovar Typhimurium. Using this murine model, we previously characterized the interactions between Salmonella Typhimurium and host cells in the gallbladder and showed that this pathogen can successfully invade gallbladder epithelial cells and proliferate. Additionally, we showed that Salmonella Typhimurium can use bile phospholipids to grow at high rates. These abilities are likely important for quick colonization of the gallbladder during typhoid fever and further pathogen dissemination through fecal shedding. To further characterize the interactions between Salmonella and the gallbladder environment, we compared the transcriptomes of Salmonella cultures grown in LB broth or physiological murine bile. Our data showed that many genes involved in bacterial central metabolism are affected by bile, with the citric acid cycle being repressed and alternative respiratory systems being activated. Additionally, our study revealed a new aspect of Salmonella interactions with bile through the identification of the global regulator phoP as a bile-responsive gene. Repression of phoP expression could also be achieved using physiological, but not commercial, bovine bile. The biological activity does not involve PhoPQ sensing of a bile component and is not caused by bile acids, the most abundant organic components of bile. Bioactivity-guided purification allowed the identification of a subset of small molecules from bile that can elicit full activity; however, a single compound with phoP inhibitory activity could not be isolated, suggesting that multiple molecules may act in synergy to achieve this effect. Due to the critical role of phoP in Salmonella virulence, further studies in this area will likely reveal aspects of the interaction between Salmonella and bile that are relevant to disease. PMID:22366421

Blood culture-PCR to optimise typhoid fever diagnosis after controlled human infection identifies frequent asymptomatic cases and evidence of primary bacteraemia.

PubMed

Darton, Thomas C; Zhou, Liqing; Blohmke, Christoph J; Jones, Claire; Waddington, Claire S; Baker, Stephen; Pollard, Andrew J

2017-04-01

Improved diagnostics for typhoid are needed; a typhoid controlled human infection model may accelerate their development and translation. Here, we evaluated a blood culture-PCR assay for detecting infection after controlled human infection with S. Typhi and compared test performance with optimally performed blood cultures. Culture-PCR amplification of blood samples was performed alongside daily blood culture in 41 participants undergoing typhoid challenge. Study endpoints for typhoid diagnosis (TD) were fever and/or bacteraemia. Overall, 24/41 (59%) participants reached TD, of whom 21/24 (86%) had ≥1 positive blood culture (53/674, 7.9% of all cultures) or 18/24 (75%) had ≥1 positive culture-PCR assay result (57/684, 8.3%). A further five non-bacteraemic participants produced culture-PCR amplicons indicating infection; overall sensitivity/specificity of the assay compared to the study endpoints were 70%/65%. We found no significant difference between blood culture and culture-PCR methods in ability to identify cases (12 mismatching pairs, p = 0.77, binomial test). Clinical and stool culture metadata demonstrated that additional culture-PCR amplification positive individuals likely represented true cases missed by blood culture, suggesting the overall attack rate may be 30/41 (73%) rather than 24/41 (59%). Several participants had positive culture-PCR results soon after ingesting challenge providing new evidence for occurrence of an early primary bacteraemia. Overall the culture-PCR assay performed well, identifying extra typhoid cases compared with routine blood culture alone. Despite limitations to widespread field-use, the benefits of increased diagnostic yield, reduced blood volume and faster turn-around-time, suggest that this assay could enhance laboratory typhoid diagnostics in research applications and high-incidence settings. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Variable Number of Tandem Repeats in Salmonella enterica subsp. enterica for Typing Purposes

PubMed Central

Ramisse, Vincent; Houssu, Perrine; Hernandez, Eric; Denoeud, France; Hilaire, Valérie; Lisanti, Olivier; Ramisse, Françoise; Cavallo, Jean-Didier; Vergnaud, Gilles

2004-01-01

The genomic sequences of Salmonella enterica subsp. enterica strains CT18, Ty2 (serovar Typhi), and LT2 (serovar Typhimurium) were analyzed for potential variable number tandem repeats (VNTRs). A multiple-locus VNTR analysis (MLVA) of 99 strains of S. enterica supsp. enterica based on 10 VNTRs distinguished 52 genotypes and placed them into four groups. All strains tested were independent human isolates from France and did not reflect isolates from outbreak episodes. Of these 10 VNTRs, 7 showed variability within serovar Typhi, whereas 1 showed variability within serovar Typhimurium. Four VNTRs showed high Nei's diversity indices (DIs) of 0.81 to 0.87 within serovar Typhi (n = 27). Additionally, three of these more variable VNTRs showed DIs of 0.18 to 0.58 within serovar Paratyphi A (n = 10). The VNTR polymorphic site within multidrug-resistant (MDR) serovar Typhimurium isolates (n = 39; resistance to ampicillin, chloramphenicol, spectinomycin, sulfonamides, and tetracycline) showed a DI of 0.81. Cluster analysis not only identified three genetically distinct groups consistent with the present serovar classification of salmonellae (serovars Typhi, Paratyphi A, and Typhimurium) but also discriminated 25 subtypes (93%) within serovar Typhi isolates. The analysis discriminated only eight subtypes within serovar Typhimurium isolates resistant to ampicillin, chloramphenicol, spectinomycin, sulfonamides, and tetracycline, possibly reflecting the emergence in the mid-1990s of the DT104 phage type, which often displays such an MDR spectrum. Coupled with the ongoing improvements in automated procedures offered by capillary electrophoresis, use of these markers is proposed in further investigations of the potential of MLVA in outbreaks of salmonellosis, especially outbreaks of typhoid fever. PMID:15583305

Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a-based prime-boost immunization strategy.

PubMed

Baillie, Leslie W J; Rodriguez, Ana L; Moore, Stephen; Atkins, Helen S; Feng, Chiguang; Nataro, James P; Pasetti, Marcela F

2008-11-11

We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [Stokes MG, Titball RW, Neeson BN, et al. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infect Immun 2007;75(April (4)):1827-34]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax.

Comparative genomics of transport proteins in probiotic and pathogenic Escherichia coli and Salmonella enterica strains.

PubMed

Do, Jimmy; Zafar, Hassan; Saier, Milton H

2017-06-01

Escherichia coli is a genetically diverse species that can be pathogenic, probiotic, commensal, or a harmless laboratory strain. Pathogenic strains of E. coli cause urinary tract infections, diarrhea, hemorrhagic colitis, and pyelonephritis, while the two known probiotic E. coli strains combat inflammatory bowel disease and play a role in immunomodulation. Salmonella enterica, a close relative of E. coli, includes two important pathogenic serovars, Typhi and Typhimurium, causing typhoid fever and enterocolitis in humans, respectively, with the latter strain also causing a lethal typhoid fever-like disease in mice. In this study, we identify the transport systems and their substrates within seven E. coli strains: two probiotic strains, two extracellular pathogens, two intracellular pathogens, and K-12, as well as the two intracellular pathogenic S. enterica strains noted above. Transport systems characteristic of each probiotic or pathogenic species were thus identified, and the tabulated results obtained with all of these strains were compared. We found that the probiotic and pathogenic strains generally contain more iron-siderophore and sugar transporters than E. coli K-12. Pathogens have increased numbers of pore-forming toxins, protein secretion systems, decarboxylation-driven Na + exporters, electron flow-driven monovalent cation exporters, and putative transporters of unknown function compared to the probiotic strains. Both pathogens and probiotic strains encode metabolite transporters that reflect their intracellular versus extracellular environments. The results indicate that the probiotic strains live extracellularly. It seems that relatively few virulence factors can convert a beneficial or commensal microorganism into a pathogen. Taken together, the results reveal the distinguishing features of these strains and provide a starting point for future engineering of beneficial enteric bacteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balakrishna, A.M.; Saxena, A.; Mok, H. Y.-K.

The type IVb pilus of the enteropathogenic bacteria Salmonella typhi is a major adhesion factor during the entry of this pathogen into gastrointestinal epithelial cells. Its target of adhesion is a stretch of 10 residues from the first extracellular domain of cystic fibrosis transmembrane conductance regulator (CFTR). The crystal structure of the N-terminal 25 amino acid deleted S. typhi native PilS protein ({Delta}PilS), which makes the pilus, was determined at 1.9 {angstrom} resolution by the multiwavelength anomalous dispersion method. Also, the structure of the complex of {Delta}PilS and a target CFTR peptide, determined at 1.8 {angstrom}, confirms that residues 113-117more » (NKEER) of CFTR are involved in binding with the pilin protein and gives us insight on the amino acids that are essential for binding. Furthermore, we have also explored the role of a conserved disulfide bridge in pilus formation. The subunit structure and assembly architecture are crucial for understanding pilus functions and designing suitable therapeutics against typhoid.« less

Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting

PubMed Central

Andrews, Jason R.; Prajapati, Krishna G.; Eypper, Elizabeth; Shrestha, Poojan; Shakya, Mila; Pathak, Kamal R.; Joshi, Niva; Tiwari, Priyanka; Risal, Manisha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Wen, Shawn; Smith, Amy B.; Maru, Duncan; Basnyat, Buddha; Baker, Stephen; Farrar, Jeremy; Ryan, Edward T.; Hohmann, Elizabeth; Arjyal, Amit

2013-01-01

Background In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Methodology/Principal Findings Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%–97.0%) and 96.0% (92.7%–98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. Conclusions/Significance A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories. PMID:23853696

A Randomized Controlled Comparison of Azithromycin and Ofloxacin for Treatment of Multidrug-Resistant or Nalidixic Acid-Resistant Enteric Fever

PubMed Central

Chinh, Nguyen Tran; Parry, Christopher M.; Ly, Nguyen Thi; Ha, Huynh Duy; Thong, Mai Xuan; Diep, To Song; Wain, John; White, Nicholas J.; Farrar, Jeremy J.

2000-01-01

To examine the efficacy and safety of short courses of azithromycin and ofloxacin for treating multidrug-resistant (MDR, i.e., resistant to chloramphenicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxacin (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in an open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolled in the study (86 with Salmonella enterica serovar Typhi and 2 with S. enterica serovar Paratyphi A). Of these, 44 received azithromycin and 44 ofloxacin. A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC90 (range) of azithromycin was 8 (4 to 16) μg/ml for the isolates. The MIC90 (range) of ofloxacin for the nalidixic acid-sensitive isolates was 0.03 (0.015 to 0.06) μg/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) μg/ml. There was no significant difference in the overall clinical cure rate with ofloxacin and azithromycin (38 of 44 [86.4%] versus 42 of 44 [95.5%]; P = 0.27) or in the patients infected with nalidixic acid-resistant typhoid (17 of 21 [81.0%] versus 24 of 25 [96.0%]; P = 0.16). However, patients with nalidixic acid-resistant typhoid treated with ofloxacin had a longer fever clearance time compared with those treated with azithromycin (174 [60 to 264] versus 135 [72 to 186] h; P = 0.004) and had positive fecal cultures after the end of treatment (7 of 17 [41%] versus 0 of 19 [0%]; P = 0.002). Both antibiotics were well tolerated. A 5-day course of azithromycin was effective for the treatment of enteric fever due to MDR and nalidixic-acid-resistant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfactory for these strains. PMID:10858343

The relationship between infecting dose and severity of disease in reported outbreaks of Salmonella infections.

PubMed Central

Glynn, J. R.; Bradley, D. J.

1992-01-01

The relationship between size of the infecting dose and severity of the resulting disease has been investigated for salmonella infections by reanalysis of data within epidemics for 32 outbreaks, and comparing data between outbreaks for 68 typhoid epidemics and 49 food-poisoning outbreaks due to salmonellas. Attack rate, incubation period, amount of infected food consumed and type of vehicle are used as proxy measures of infecting dose, while case fatality rates for typhoid and case hospitalization rates for food poisoning salmonellas were used to assess severity. Limitations of the data are discussed. Both unweighted and logit analysis models are used. There is no evidence for a dose-severity relationship for Salmonella typhi, but evidence of a correlation between dose and severity is available from within-epidemic or between-epidemic analysis, or both, for Salmonella typhimurium, S. enteritidis, S. infantis, S. newport, and S. thompson. The presence of such a relationship affects the way in which control interventions should be assessed. PMID:1468522

Typhoid fever with severe abdominal pain: diagnosis and clinical findings using abdomen ultrasonogram, hematology-cell analysis and the Widal test.

PubMed

Arjunan, Maripandi; Al-Salamah, Ali A

2010-10-04

A six-year-old boy with high-grade fever and abdominal pain in the epigastric region was examined with ultrasonogram of the abdomen. Hematology-cell analysis, serology (Widal test), urine analysis, and blood cultures were also performed. The ultrasonogram was helpful for the identification of multiple organ involvement with Salmonella typhi. The results revealed mild hepatosplenomegaly, minimal ascitis, and mesenteric lympoadenopathy. Hematological analysis showed a white blood count of 6,300 cells mL-1; a red blood cell count of 4.54 million/cu mm. The erythrocyte sedimentation rate (ESR) was 24 mm/1 hr; hemoglobin level of 11.5 g/dl; and a platelet count of 206,000 cells/mL. The patient's serum was agglutinated with lipopolysaccharide (TO), the titre value was 1:320 dilution, and flagellar antigen (TH) titre was 1:640. The patient was diagnosed with typhoid fever. Ceftriaxone was given intravenously for five days and the patient fully recovered.

World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010

PubMed Central

Havelaar, Arie H.; Kirk, Martyn D.; Torgerson, Paul R.; Gibb, Herman J.; Hald, Tine; Lake, Robin J.; Praet, Nicolas; Bellinger, David C.; de Silva, Nilanthi R.; Gargouri, Neyla; Speybroeck, Niko; Cawthorne, Amy; Mathers, Colin; Stein, Claudia; Angulo, Frederick J.; Devleesschauwer, Brecht

2015-01-01

Illness and death from diseases caused by contaminated food are a constant threat to public health and a significant impediment to socio-economic development worldwide. To measure the global and regional burden of foodborne disease (FBD), the World Health Organization (WHO) established the Foodborne Disease Burden Epidemiology Reference Group (FERG), which here reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards. We find that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis. The most frequent causes of foodborne illness were diarrheal disease agents, particularly norovirus and Campylobacter spp. Diarrheal disease agents, especially non-typhoidal Salmonella enterica, were also responsible for the majority of deaths due to FBD. Other major causes of FBD deaths were Salmonella Typhi, Taenia solium and hepatitis A virus. The global burden of FBD caused by the 31 hazards in 2010 was 33 million Disability Adjusted Life Years (DALYs); children under five years old bore 40% of this burden. The 14 subregions, defined on the basis of child and adult mortality, had considerably different burdens of FBD, with the greatest falling on the subregions in Africa, followed by the subregions in South-East Asia and the Eastern Mediterranean D subregion. Some hazards, such as non-typhoidal S. enterica, were important causes of FBD in all regions of the world, whereas others, such as certain parasitic helminths, were highly localised. Thus, the burden of FBD is borne particularly by children under five years old–although they represent only 9% of the global population–and people living in low-income regions of the world. These estimates are conservative, i.e., underestimates rather than overestimates; further studies are needed to address the data gaps and limitations of the study. Nevertheless, all stakeholders can contribute to improvements in food safety throughout the food chain by incorporating these estimates into policy development at national and international levels. PMID:26633896

World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010.

PubMed

Havelaar, Arie H; Kirk, Martyn D; Torgerson, Paul R; Gibb, Herman J; Hald, Tine; Lake, Robin J; Praet, Nicolas; Bellinger, David C; de Silva, Nilanthi R; Gargouri, Neyla; Speybroeck, Niko; Cawthorne, Amy; Mathers, Colin; Stein, Claudia; Angulo, Frederick J; Devleesschauwer, Brecht

2015-12-01

Illness and death from diseases caused by contaminated food are a constant threat to public health and a significant impediment to socio-economic development worldwide. To measure the global and regional burden of foodborne disease (FBD), the World Health Organization (WHO) established the Foodborne Disease Burden Epidemiology Reference Group (FERG), which here reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards. We find that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis. The most frequent causes of foodborne illness were diarrheal disease agents, particularly norovirus and Campylobacter spp. Diarrheal disease agents, especially non-typhoidal Salmonella enterica, were also responsible for the majority of deaths due to FBD. Other major causes of FBD deaths were Salmonella Typhi, Taenia solium and hepatitis A virus. The global burden of FBD caused by the 31 hazards in 2010 was 33 million Disability Adjusted Life Years (DALYs); children under five years old bore 40% of this burden. The 14 subregions, defined on the basis of child and adult mortality, had considerably different burdens of FBD, with the greatest falling on the subregions in Africa, followed by the subregions in South-East Asia and the Eastern Mediterranean D subregion. Some hazards, such as non-typhoidal S. enterica, were important causes of FBD in all regions of the world, whereas others, such as certain parasitic helminths, were highly localised. Thus, the burden of FBD is borne particularly by children under five years old-although they represent only 9% of the global population-and people living in low-income regions of the world. These estimates are conservative, i.e., underestimates rather than overestimates; further studies are needed to address the data gaps and limitations of the study. Nevertheless, all stakeholders can contribute to improvements in food safety throughout the food chain by incorporating these estimates into policy development at national and international levels.

Measurement of Typhi Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency.

PubMed

Evans, C; Bateman, E; Steven, R; Ponsford, M; Cullinane, A; Shenton, C; Duthie, G; Conlon, C; Jolles, S; Huissoon, A P; Longhurst, H J; Rahman, T; Scott, C; Wallis, G; Harding, S; Parker, A R; Ferry, B L

2018-01-29

Vaccine-specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi ® , a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi-centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) calibrated to an affinity-purified Typhi Vi IgG preparation. Intra- and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99-1·00; R 2  > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations  > 7·4 U/ml, the concentration range was 7·7-167 U/ml. In antibody-deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post-vaccination was 107 U/ml (range 31-542 U/ml). Eight of eight patients (100%) had post-vaccination concentration increases of at least threefold and six of eight (75%) of at least 10-fold. In an antibody-deficient population (n = 23), only 30% had post-vaccination concentration increases of at least threefold and 10% of at least 10-fold. The antibody responses to Pneumovax II and Typhim Vi ® correlated. We conclude that IgG responses to Typhim Vi ® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies. © 2018 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the Live Salmonella Oral Vaccine Vector Ty21a

PubMed Central

Osorio, Manuel; Takeda, Kazuyo; Stibitz, Scott; Kopecko, Dennis J.

2017-01-01

ABSTRACT We have been exploring the use of the live attenuated Salmonella enterica serovar Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression and delivery of multiple foreign antigens, including Shigella O-antigens. In this study, we separately cloned genes necessary for the biosynthesis of the Shigella flexneri serotype 2a and 3a O-antigens, which have been shown to provide broad cross-protection to multiple disease-predominant S. flexneri serotypes. The cloned S. flexneri 2a rfb operon, along with bgt and gtrII, contained on the SfII bacteriophage, was sufficient in Ty21a to express the heterologous S. flexneri 2a O-antigen containing the 3,4 antigenic determinants. Further, this rfb operon, along with gtrA, gtrB, and gtrX contained on the Sfx bacteriophage and oac contained on the Sf6 bacteriophage, was sufficient to express S. flexneri 3a O-antigen containing the 6, 7, and 8 antigenic determinants. Ty21a, with these plasmid-carried or chromosomally inserted genes, demonstrated simultaneous and stable expression of homologous S. Typhi O-antigen plus the heterologous S. flexneri O-antigen. Candidate Ty21a vaccine strains expressing heterologous S. flexneri 2a or 3a lipopolysaccharide (LPS) elicited significant serum antibody responses against both homologous S. Typhi and heterologous Shigella LPS and protected mice against virulent S. flexneri 2a or 3a challenges. These new S. flexneri 2a and 3a O-antigen-expressing Ty21a vaccine strains, together with our previously constructed Ty21a strains expressing Shigella sonnei or Shigella dysenteriae 1 O-antigens, have the potential to be used together for simultaneous protection against the predominant causes of shigellosis worldwide as well as against typhoid fever. PMID:29046309

Molecular epidemiology of fluoroquinolone resistant Salmonella in Africa: A systematic review and meta-analysis.

PubMed

Tadesse, Getachew; Tessema, Tesfaye S; Beyene, Getenet; Aseffa, Abraham

2018-01-01

Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of this study were to assess the heterogeneity, estimate pooled proportions and describe the preponderance of FQ-resistance determinants in typhoidal and non-typhoidal Salmonella (NTS) isolates of Africa. Genetic and phenotypic data on 6103 Salmonella isolates were considered. Meta- and frequency analyses were performed depending on the number of studies by category, number of isolates and risks of bias. A random effects model was used to assess heterogeneity and estimate pooled proportions. Relative and cumulative frequencies were calculated to describe the overall preponderance of FQ-resistance determinants in quinolone resistant isolates. The pooled proportion of gyrA mutants (Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Salmonella enterica serovar Enteritidis) was estimated at 5.7% (95% Confidence interval (CI) = 2.6, 9.8; Tau squared (T2) = 0.1105), and was higher in S. Typhi than in S. Typhimurium (odds ratio (OR) = 3.3, 95%CI = 2, 5.7). The proportions of each of gyrB and parC mutants, and strains with Plasmid Mediated Quinolone Resistance genes (qnrA, qnrB and qnrS) were low (≤ 0.3%). Overall, 23 mutant serotypes were identified, and most strains had mutations at codons encoding Ser83 and Asp87 of gyrA (82%, 95%CI = 78, 86). Mutations at gyrA appear to account for ciprofloxacin non-susceptibility in most clinical Salmonella strains in Africa. The estimates could be harnessed to develop a mismatch-amplification mutation-assay for the detection of FQ-resistant strains in Africa.

Molecular epidemiology of fluoroquinolone resistant Salmonella in Africa: A systematic review and meta-analysis

PubMed Central

Tessema, Tesfaye S.; Beyene, Getenet; Aseffa, Abraham

2018-01-01

Background Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of this study were to assess the heterogeneity, estimate pooled proportions and describe the preponderance of FQ-resistance determinants in typhoidal and non-typhoidal Salmonella (NTS) isolates of Africa. Methods Genetic and phenotypic data on 6103 Salmonella isolates were considered. Meta- and frequency analyses were performed depending on the number of studies by category, number of isolates and risks of bias. A random effects model was used to assess heterogeneity and estimate pooled proportions. Relative and cumulative frequencies were calculated to describe the overall preponderance of FQ-resistance determinants in quinolone resistant isolates. Results The pooled proportion of gyrA mutants (Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Salmonella enterica serovar Enteritidis) was estimated at 5.7% (95% Confidence interval (CI) = 2.6, 9.8; Tau squared (T2) = 0.1105), and was higher in S. Typhi than in S. Typhimurium (odds ratio (OR) = 3.3, 95%CI = 2, 5.7). The proportions of each of gyrB and parC mutants, and strains with Plasmid Mediated Quinolone Resistance genes (qnrA, qnrB and qnrS) were low (≤ 0.3%). Overall, 23 mutant serotypes were identified, and most strains had mutations at codons encoding Ser83 and Asp87 of gyrA (82%, 95%CI = 78, 86). Conclusions Mutations at gyrA appear to account for ciprofloxacin non-susceptibility in most clinical Salmonella strains in Africa. The estimates could be harnessed to develop a mismatch-amplification mutation-assay for the detection of FQ-resistant strains in Africa. PMID:29432492

O-Serotype Conversion in Salmonella Typhimurium Induces Protective Immune Responses against Invasive Non-Typhoidal Salmonella Infections.

PubMed

Li, Pei; Liu, Qing; Luo, Hongyan; Liang, Kang; Yi, Jie; Luo, Ying; Hu, Yunlong; Han, Yue; Kong, Qingke

2017-01-01

Salmonella infections remain a big problem worldwide, causing enteric fever by Salmonella Typhi (or Paratyphi) or self-limiting gastroenteritis by non-typhoidal Salmonella (NTS) in healthy individuals. NTS may become invasive and cause septicemia in elderly or immuno-compromised individuals, leading to high mortality and morbidity. No vaccines are currently available for preventing NTS infection in human. As these invasive NTS are restricted to several O-antigen serogroups including B1, D1, C1, and C2, O-antigen polysaccharide is believed to be a good target for vaccine development. In this study, a strategy of O-serotype conversion was investigated to develop live attenuated S . Typhimurium vaccines against the major serovars of NTS infections. The immunodominant O4 serotype of S . Typhimurium was converted into O9, O7, and O8 serotypes through unmarked chromosomal deletion-insertion mutations. O-serotype conversion was confirmed by LPS silver staining and western blotting. All O-serotype conversion mutations were successfully introduced into the live attenuated S . Typhimurium vaccine S738 (Δ crp Δ cya ) to evaluate their immunogenicity in mice model. The vaccine candidates induced high amounts of heterologous O-polysaccharide-specific functional IgG responses. Vaccinated mice survived a challenge of 100 times the 50% lethality dose (LD 50 ) of wild-type S . Typhimurium. Protective efficacy against heterologous virulent Salmonella challenges was highly O-serotype related. Furthermore, broad-spectrum protection against S . Typhimurium, S . Enteritidis, and S . Choleraesuis was observed by co-vaccination of O9 and O7 O-serotype-converted vaccine candidates. This study highlights the strategy of expressing heterologous O-polysaccharides via genetic engineering in developing live attenuated S . Typhimurium vaccines against NTS infections.

CRISPR Is an Optimal Target for the Design of Specific PCR Assays for Salmonella enterica Serotypes Typhi and Paratyphi A

PubMed Central

Fabre, Laetitia; Le Hello, Simon; Roux, Chrystelle; Issenhuth-Jeanjean, Sylvie; Weill, François-Xavier

2014-01-01

Background Serotype-specific PCR assays targeting Salmonella enterica serotypes Typhi and Paratyphi A, the causal agents of typhoid and paratyphoid fevers, are required to accelerate formal diagnosis and to overcome the lack of typing sera and, in some situations, the need for culture. However, the sensitivity and specificity of such assays must be demonstrated on large collections of strains representative of the targeted serotypes and all other bacterial populations producing similar clinical symptoms. Methodology Using a new family of repeated DNA sequences, CRISPR (clustered regularly interspaced short palindromic repeats), as a serotype-specific target, we developed a conventional multiplex PCR assay for the detection and differentiation of serotypes Typhi and Paratyphi A from cultured isolates. We also developed EvaGreen-based real-time singleplex PCR assays with the same two sets of primers. Principal findings We achieved 100% sensitivity and specificity for each protocol after validation of the assays on 188 serotype Typhi and 74 serotype Paratyphi A strains from diverse genetic groups, geographic origins and time periods and on 70 strains of bacteria frequently encountered in bloodstream infections, including 29 other Salmonella serotypes and 42 strains from 38 other bacterial species. Conclusions The performance and convenience of our serotype-specific PCR assays should facilitate the rapid and accurate identification of these two major serotypes in a large range of clinical and public health laboratories with access to PCR technology. These assays were developed for use with DNA from cultured isolates, but with modifications to the assay, the CRISPR targets could be used in the development of assays for use with clinical and other samples. PMID:24498453

Sero-efficacy of Vi-polysaccharide tetanus-toxoid typhoid conjugate vaccine (Typbar-TCV).

PubMed

Voysey, Merryn; Pollard, Andrew J

2018-01-17

Salmonella Typhi is the major cause of enteric fever in lower income countries. New conjugate vaccines show promise as public health interventions, however there are no efficacy data available from endemic areas. Data were obtained from a previously published phase 3 randomised controlled trial comparing Vi-polysaccharide tetanus-toxoid conjugate vaccine (Typbar-TCV; Bharat Biotech Intl Ltd, India): (Vi-TT) with Vi-polysaccharide (Typbar; Bharat Biotech Intl Ltd, India): (Vi-PS) in participants aged 2- 45 years. An additional open-label arm administered Vi-TT to children aged 6 months to 23 months. The proportion of participants with presumed clinical or subclinical infection ('seroincidence'), was determined using mixture models and compared using relative risks. 81/387 (21%) participants were classified as having presumed typhoid infection during the 2 year period post-vaccination. Seroincidence was lower in those randomised to Vi-TT than Vi-PS in those aged 2-45 years; 21/155 (13.5%) vs 47/129 (36.4%); RR 0.372 (95%CI 0.235-0.588), p<0.0001 and in those aged 2-15 years RR 0.424 (95%CI 0.231-0.778), p=0.0039. There was no difference in seroincidence in those receiving Vi-TT aged 2-45 years and those aged 6-23 months; 21/155 (13.5%) vs 13/103 (12.6%); RR 1.073 (0.563, 2.046), p=0.8293. Vaccine seroefficacy was 85% (95%CI 80-88%). This is the first field estimate of the seroefficacy of a Vi-TT vaccine and shows that Typbar TCV substantially reduces the number of serologically defined (sub)clinical infections in infants, children and adults. These results support the recent World Health Organisation recommendations for deployment of typhoid conjugate vaccines in high burden areas. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Typhoid fever

MedlinePlus

Typhoid fever is an infection that causes diarrhea and a rash . It is most commonly caused due to ... in their stools for years, spreading the disease. Typhoid fever is common in developing countries. Most cases in ...

Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.

PubMed

Küçük, Öznur; Biçer, Suat; Ugraş, Meltem; Çöl, Defne; Giray, Tuba; Çiler Erdag, Gülay; Gürol, Yeşim; Yilmaz, Gülden; Yalvaç, Zerrin; Vitrinel, Ayça; Kaspar, Çigdem

2016-09-01

The purpose of this study was to evaluate the clinical and laboratory data of children with acute gastroenteritis caused by non-typhoid Salmonella spp. infections. Clinical (demographic data, symptoms and findings) and laboratory data (stool microscopy, rapid antigen tests, culture, multiplex polymerase chain reaction and blood test results) of children with acute gastroenteritis caused by non-typhoid Salmonella spp. between January 2010 and October 2012 were evaluated. Differences between the groups for categorical variables were estimated with a chi-square or Fisher exact test; for continuous variables with two independent samples a t test was used. P values < 0.05 were considered statistically significant. Sixty-seven children, 39 (58.2%) males and 28 (41.8%) females aged between 1 - 16 years (mean ± SD: 4.64 ± 2.91), were diagnosed with acute bacterial gastroenteritis caused by non-typhoid Salmonella spp. The main serotypes are Salmonella enteritidis (85%) and Salmonella typhimurium (7.5%). The presenting symptoms were diarrhoea (95.5%), fever (61.1%), vomiting (34.3%), abdominal pain (32.8%), loss of appetite (7.4%) and malaise (7.4%). Fever and dehydration (moderate and/or severe) were detected in 11 (16.4%) patients. The mean leukocyte count was 10.930/μL [95% confidence interval (CI), SD: ± 5.710/μL], neutrophil count was 7.880/μL (95% CI, SD: ± 4.960/μL), CRP was 64.16 mg/L (95% CI, SD: ± 76.24 mg/L), and erythrocyte sedimentation rate was 34.72 mm/hour (95% CI, SD: ± 13.64 mm/h). Stool microscopy was positive for leukocytes in 18 patients (26.8%). The definitive diagnosis was made with positive stool culture (n = 65) and/or PCR test (n = 4). Viral antigen positivity was detected in 10 patients (14.9%), evaluated as viral co-infection and false positive results. Antibiotic therapy and hospitalization were required in 26 (38.8%) and 23 (34.3%) patients, respectively. Salmonella carriage was detected in one patient (1.5%). Bloody diarrhoea, leukocytes in stool with an increased erythrocyte sedimentation rate and a CRP level without overt leukocytosis may indicate Salmonella infection. Viral antigens may cause false positive results in fast antigen tests in cases where clinical and laboratory findings indicate bacterial aetiology. Stool culture is a reference method in diagnosis whereas some agents may be detected via molecular techniques (polymerase chain reaction) in spite of negative culture. Multiplex polymerase chain reaction may be used to detect Salmonella spp. and may reveal false positivity for viruses as well as the detection of other bacteria.

Diagnostics for invasive Salmonella infections: current challenges and future directions

PubMed Central

Andrews, Jason R.; Ryan, Edward T.

2015-01-01

Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results in frequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics. PMID:25937611

Diagnostics for invasive Salmonella infections: Current challenges and future directions.

PubMed

Andrews, Jason R; Ryan, Edward T

2015-06-19

Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results in frequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics. Copyright © 2015. Published by Elsevier Ltd.

Cases of typhoid fever in Copenhagen region: a retrospective study of presentation and relapse.

PubMed

Barrett, Freja Cecille; Knudsen, Jenny Dahl; Johansen, Isik Somuncu

2013-08-11

Typhoid fever is a systemic illness which in high-income countries mainly affects travellers. The incidence is particularly high on the Indian subcontinent. Travellers who visit friends and relatives (VFR) have been shown to have a different risk profile than others. We wished to identify main characteristics for travellers infected with S. Typhi considering both clinical and laboratory findings in order to provide for faster and better diagnostics in the future. The outcome of treatment, especially concerning relapse, was evaluated as well. Retrospectively collected data from 19 adult cases of typhoid fever over a 5-year period at the Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Denmark. The patients were young adults, presenting with symptoms within a month after travelling. 84% were returned from travelling in the Indian subcontinent. 17 out of 19 patients were VFR-travellers. The main symptoms were fever (100%), gastrointestinal symptoms (84%), headache (58%) and dry cough (26%). Laboratory findings showed elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH) in all cases and elevated alanine transaminase (ALAT) in 47% of cases. In primary cases 4 isolates were fully susceptible to ciprofloxacin, the remaining were intermediate susceptible. Relapse occurred in 37% of the cases and only in cases where the patient was infected by a strain with intermediate susceptibility. Better pre-travel counselling should be given to VFR-travellers. The main symptoms and laboratory findings confirm previous findings. The relapse rate was unexpected high and could be correlated to ciprofloxacin-resistance.

Immunization with the conjugate vaccine Vi-CRM₁₉₇ against Salmonella typhi induces Vi-specific mucosal and systemic immune responses in mice.

PubMed

Fiorino, Fabio; Ciabattini, Annalisa; Rondini, Simona; Pozzi, Gianni; Martin, Laura B; Medaglini, Donata

2012-09-21

Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM₁₉₇, composed of the polysaccharide antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM₁₉₇, is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM₁₉₇. The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM₁₉₇ was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM₁₉₇ and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM₁₉₇ as a promising candidate vaccine against Salmonella Typhi. Copyright © 2012 Elsevier Ltd. All rights reserved.

MILLS-REINCKE PHENOMENON AND TYPHOID CONTROL BY VACCINE

PubMed Central

McGee, Harold G.

1920-01-01

Assuming typhoid to be an index of conditions favoring other causes of death, this author calls attention to the likelihood that anti-typhoid vaccination, by attacking typhoid alone, really masks sanitary conditions and may permit unnecessary deaths. Complete eradication of typhoid through vaccination would not affect the three other deaths suggested by the Mills-Reincke hypothesis. PMID:18010339

Salmonella Extracellular Matrix Components Influence Biofilm Formation and Gallbladder Colonization.

PubMed

Adcox, Haley E; Vasicek, Erin M; Dwivedi, Varun; Hoang, Ky V; Turner, Joanne; Gunn, John S

2016-11-01

Salmonella enterica serovar Typhi, the causative agent of typhoid fever in humans, forms biofilms encapsulated by an extracellular matrix (ECM). Biofilms facilitate colonization and persistent infection in gallbladders of humans and mouse models of chronic carriage. Individual roles of matrix components have not been completely elucidated in vitro or in vivo To examine individual functions, strains of Salmonella enterica serovar Typhimurium, the murine model of S Typhi, in which various ECM genes were deleted or added, were created to examine biofilm formation, colonization, and persistence in the gallbladder. Studies show that curli contributes most significantly to biofilm formation. Expression of Vi antigen decreased biofilm formation in vitro and virulence and bacterial survival in vivo without altering the examined gallbladder pro- or anti-inflammatory cytokines. Oppositely, loss of all ECM components (ΔwcaM ΔcsgA ΔyihO ΔbcsE) increased virulence and bacterial survival in vivo and reduced gallbladder interleukin-10 (IL-10) levels. Colanic acid and curli mutants had the largest defects in biofilm-forming ability and contributed most significantly to the virulence increase of the ΔwcaM ΔcsgA ΔyihO ΔbcsE mutant strain. While the ΔwcaM ΔcsgA ΔyihO ΔbcsE mutant was not altered in resistance to complement or growth in macrophages, it attached and invaded macrophages better than the wild-type (WT) strain. These data suggest that ECM components have various levels of importance in biofilm formation and gallbladder colonization and that the ECM diminishes disseminated disease in our model, perhaps by reducing cell attachment/invasion and dampening inflammation by maintaining/inducing IL-10 production. Understanding how ECM components aid acute disease and persistence could lead to improvements in therapeutic treatment of typhoid fever patients. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Enteric fever in Mumbai--clinical profile, sensitivity patterns and response to antimicrobials.

PubMed

Jog, S; Soman, R; Singhal, T; Rodrigues, C; Mehta, A; Dastur, F D

2008-04-01

Enteric fever is endemic in Mumbai and its diagnosis poses several problems. Our main aim was to study the clinical profile, haematological features of culture proven typhoid cases, the antimicrobial susceptibility pattern of the isolates and the time to defervescence with the treatment received. This was a retospective chart review of all cases of culture proven enteric fever carried out at a tertiary care private hospital in Mumbai over the period January 2003 to September 2005. Culture positivity in our study was 52.6%. Sixty one percent of the isolates were Salmonella typhi while 39% were Salmonella paratyphi A. An absolute eosinopenia was seen in 76.9% of the patients. Before being admitted to the hospital, 46.2% received antibiotics. The mean time to defervescence in patients who received prior antibiotics was 4.5 days while that in those who did not receive prior antibiotics was 5.1 days. A high culture positivity despite prior or ongoing antibiotic treatment was seen. Absolute eosinophil count of 0% could be an important marker of typhoid. High prevalence of nalidixic acid resistance, a marker of resistance to fluoroquinolones was observed. Combination treatment was not found to be superior to treatment with a single antibiotic.

Typhoid fever: misuse of Widal test in Libya.

PubMed

Zorgani, Abdulaziz; Ziglam, Hisham

2014-06-11

The worldwide gold standard of diagnosing of enteric fever depends on the isolation of Salmonella enterica serovar Typhi from a patient's bone marrow and/or blood culture. In Libya clinicians are heavily dependent on the Widal test for diagnosis of enteric fever which has been used without determining the locally appropriate threshold titer, because the laboratories lack the skilled, experienced personnel and appropriate facilities to detect and serotype Salmonella isolates. To improve the diagnosis process, clinical management and reliability of public health measures, there is an urgent need for the effective training of laboratory technicians and to provide resources to culture Salmonella species according to published guidelines. Clinicians should understand the limitations of Widal test and recognize that it cannot be expected to give a reliable diagnosis.

Re-examination of immune response and estimation of anti-Vi IgG protective threshold against typhoid fever-based on the efficacy trial of Vi conjugate in young children.

PubMed

Szu, Shousun C; Klugman, Keith P; Hunt, Steven

2014-04-25

The capsular polysaccharide of Salmonella enterica serovar Typhi, Vi antigen, is an essential virulence factor and a protective antigen. Similar to other polysaccharide vaccines, the protective action of Vi, both to the polysaccharide alone or when presented as a conjugate, is mediated by serum IgG Vi antibodies. The evaluation of Vi capsular polysaccharide based vaccines to prevent typhoid fever would be significantly facilitated by the identification of a "protective level" of serum antibodies to Vi antigen. The protective level of anti-Vi IgG against typhoid fever was derived from the protective efficacy and immune response of a Vi-rEPA conjugate vaccine efficacy trial. The estimation was derived by two methods: correlation of the percent efficacy and the antibody distribution profile in the vaccine group at a given period of observation, and use of the relative ratio of anti-Vi IgG levels between the vaccine and placebo groups greater or equal to the Relative Risk of typhoid fever used in the efficacy determination. Both methods predicted a similar range of a minimum protective level of anti-Vi IgG between 1.4 and 2.0μg/ml (short term threshold). When applying a protective threshold of 10μg/ml at 6 months post immunization, an IgG level in excess of 1.4μg/ml was achieved by 90% of children at 46 months post immunization, consistent with an 89% level of protection over the duration of the study. We thus suggest that the proportion of children with Vi IgG>10μg/ml (long term threshold) 6 months after immunization may reflect the proportion protected over at least a 4 year period. The current assignment of an anti-Vi IgG protective level may be of value when evaluating vaccine performance of future Vi conjugate vaccines. Published by Elsevier Ltd.

A typhoid fever outbreak in a slum of South Dumdum municipality, West Bengal, India, 2007: evidence for foodborne and waterborne transmission.

PubMed

Bhunia, Rama; Hutin, Yvan; Ramakrishnan, Ramachandran; Pal, Nishith; Sen, Tapas; Murhekar, Manoj

2009-04-27

In April 2007, a slum of South Dumdum municipality, West Bengal reported an increase in fever cases. We investigated to identify the agent, the source and to propose recommendations. We defined a suspected case of typhoid fever as occurrence of fever for > or = one week among residents of ward 1 of South Dumdum during February - May 2007. We searched for suspected cases in health care facilities and collected blood specimens. We described the outbreak by time, place and person. We compared probable cases (Widal positive > or = 1:80) with neighbourhood-matched controls. We assessed the environment and collected water specimens. We identified 103 suspected cases (Attack rate: 74/10,000, highest among 5-14 years old group, no deaths). Salmonella (enterica) Typhi was isolated from one of four blood specimens and 65 of 103 sera were > or = 1:80 Widal positive. The outbreak started on 13 February, peaked twice during the last week of March and second week of April and lasted till 27 April. Suspected cases clustered around three public taps. Among 65 probable cases and 65 controls, eating milk products from a sweet shop (Matched odds ratio [MOR]: 6.2, 95% confidence interval [CI]: 2.4-16, population attributable fraction [PAF]: 53%) and drinking piped water (MOR: 7.3, 95% CI: 2.5-21, PAF-52%) were associated with illness. The sweet shop food handler suffered from typhoid in January. The pipelines of intermittent non-chlorinated water supply ran next to an open drain connected with sewerage system and water specimens showed faecal contamination. The investigation suggested that an initial foodborne outbreak of typhoid led to the contamination of the water supply resulting in a secondary, waterborne wave. We educated the food handler, repaired the pipelines and ensured chlorination of the water.

Re-examination of immune response and estimation of anti-Vi IgG protective threshold against typhoid fever-based on the efficacy trial of Vi conjugate in young children

PubMed Central

Szu, Shousun C.; Klugman, Keith P.; Hunt, Steven

2014-01-01

Background The capsular polysaccharide of Salmonella enterica serovar Typhi, Vi antigen, is an essential virulence factor and a protective antigen. Similar to other polysaccharide vaccines, the protective action of Vi, both to the polysaccharide alone or when presented as a conjugate, is mediated by serum IgG Vi antibodies. The evaluation of Vi capsular polysaccharide based vaccines to prevent typhoid fever would be significantly facilitated by the identification of a “protective level” of serum antibodies to Vi antigen. Methods The protective level of anti-Vi IgG against typhoid fever was derived from the protective efficacy and immune response of a Vi-rEPA conjugate vaccine efficacy trial. The estimation was derived by two methods: correlation of the percent efficacy and the antibody distribution profile in the vaccine group at a given period of observation, and use of the relative ratio of anti-Vi IgG levels between the vaccine and placebo groups greater or equal to the Relative Risk of typhoid fever used in the efficacy determination. Results Both methods predicted a similar range of a minimum protective level of anti-Vi IgG between 1.4 and 2.0 μg/ml (short term threshold). When applying a protective threshold of 10 μg/ml at 6 months post immunization, an IgG level in excess of 1.4 μg/ml was achieved by 90% of children at 46 months post immunization, consistent with an 89% level of protection over the duration of the study. We thus suggest that the proportion of children with Vi IgG > 10 μg/ml (long term threshold) 6 months after immunization may reflect the proportion protected over at least a 4 year period. Conclusion The current assignment of an anti-Vi IgG protective level may be of value when evaluating vaccine performance of future Vi conjugate vaccines. PMID:24630869

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report

PubMed Central

2010-01-01

Introduction We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity. Case presentation As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region. Conclusion Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever. PMID:20525295

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report.

PubMed

Ezzat, Rajan Fuad; Hussein, Hiwa A; Baban, Trifa Shawkat; Rashid, Abbas Tahir; Abdullah, Khaled Musttafa

2010-06-03

We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity. As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region. Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever.

Ten years experience of Salmonella infections in Cambridge, UK.

PubMed

Matheson, Nicholas; Kingsley, Robert A; Sturgess, Katherine; Aliyu, Sani H; Wain, John; Dougan, Gordon; Cooke, Fiona J

2010-01-01

Review of all Salmonella infections diagnosed in the Cambridge area over 10 years. All Salmonella enterica isolated in the Clinical Microbiology Laboratory, Addenbrooke's Hospital between 1.1.1999 and 31.12.2008 were included. Patient demographics, serotype and additional relevant details (travel history, resistance-type, phage-type) were recorded. 1003 episodes of Salmonella gastroenteritis were confirmed by stool culture, representing 88 serotypes. Serotypes Enteritidis (59%), Typhimurium (4.7%), Virchow (2.6%), Newport (1.8%) and Braenderup (1.7%) were the 5 most common isolates. There were an additional 37 invasive Salmonella infections (32 blood cultures, 4 tissue samples, 1 CSF). 13/15 patients with Salmonella Typhi or Salmonella Paratyphi isolated from blood or faeces with an available travel history had returned from the Indian subcontinent. 8/10 S. Typhi or Paratyphi isolates tested had reduced susceptibility to fluoroquinolones (MIC > or = 0.125 mg/L). 7/21 patients with non-typhoidal Salmonella bacteraemia were known to be immunosuppressed. This study describes Salmonella serotypes circulating within a defined geographical area over a decade. Prospective molecular analysis of isolates of S. enterica by multi-locus sequence typing (MLST) and single nucleotide polymorphism (SNP) detection will determine the geo-phylogenetic relationship of isolates within our region. 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Clonal Expansion and Microevolution of Quinolone-Resistant Salmonella enterica Serotype Typhi in Vietnam from 1996 to 2004▿

PubMed Central

Le, Thi Anh Hong; Fabre, Laëtitia; Roumagnac, Philippe; Grimont, Patrick A. D.; Scavizzi, Maurice R.; Weill, François-Xavier

2007-01-01

Salmonella enterica serotype Typhi clinical isolates (n = 91) resistant to nalidixic acid (Nalr) were collected from sporadic cases and minor outbreaks throughout Vietnam between 1996 and 2004. These isolates were typed and compared by four methods: Vi phage typing, PstI ribotyping, XbaI and SpeI pulsed-field gel electrophoresis (PFGE), and single-nucleotide polymorphism (SNP) analysis. The results indicated that 65% of the isolates were not typeable by Vi phage typing. In contrast, the ribotyping and, with more accuracy, the SNP analysis methods indicated that all Nalr isolates belonged to a single clone (ribotype 3a, haplotype H58) that was found previously and that largely consisted of plasmid-encoded multidrug-resistant serotype Typhi isolates. PFGE demonstrated the occurrence of microevolution within this clone. We identified two major combined PFGE profiles: X1-S1 and X3-S6. X3-S6 predominated between 1996 and 2002 but was replaced by X1-S1 after 2002. Nevertheless, PFGE, with a Simpson's index of 0.78, was not considered an optimal discriminatory method for investigating typhoid fever outbreaks in Vietnam. The rate of quinolone resistance increased and the rate of multidrug resistance decreased during the study period. From 2002 to 2004, 80.6% of the isolates from South Vietnam were resistant only to Nal. The mechanism of Nal resistance in most of the isolates (94%) was a mutation in the quinolone resistance-determining chromosomal region of gyrA that led to the amino acid substitution Ser83Phe. No plasmid-located qnrA, qnrB, or qnrS was detected. PMID:17728470

Ebola Virus Disease

MedlinePlus

... EVD from other infectious diseases such as malaria, typhoid fever and meningitis. Confirmation that symptoms are caused by ... EVD from other infectious diseases such as malaria, typhoid fever and meningitis. Confirmation that symptoms are caused by ...

Murine Typhus

PubMed Central

Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

2012-01-01

Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

Phenotypical resistance correlation networks for 10 non-typhoidal Salmonella subpopulations in an active antimicrobial surveillance programme.

PubMed

Love, W J; Zawack, K A; Booth, J G; Gröhn, Y T; Lanzas, C

2018-06-01

Antimicrobials play a critical role in treating cases of invasive non-typhoidal salmonellosis (iNTS) and other diseases, but efficacy is hindered by resistant pathogens. Selection for phenotypical resistance may occur via several mechanisms. The current study aims to identify correlations that would allow indirect selection of increased resistance to ceftriaxone, ciprofloxacin and azithromycin to improve antimicrobial stewardship. These are medically important antibiotics for treating iNTS, but these resistances persist in non-Typhi Salmonella serotypes even though they are not licensed for use in US food animals. A set of 2875 Salmonella enterica isolates collected from animal sources by the National Antimicrobial Resistance Monitoring System were stratified in to 10 subpopulations based on serotype and host species. Collateral resistances in each subpopulation were estimated as network models of minimum inhibitory concentration partial correlations. Ceftriaxone sensitivity was correlated with other β-lactam resistances, and less commonly resistances to tetracycline, trimethoprim-sulfamethoxazole or kanamycin. Azithromycin resistance was frequently correlated with chloramphenicol resistance. Indirect selection for ciprofloxacin resistance via collateral selection appears unlikely. Density of the ACSSuT subgraph resistance aligned well with the phenotypical frequency. The current study identifies several important resistances in iNTS serotypes and further research is needed to identify the causative genetic correlations.

CROSS-REACTIONS OF ANTITYPHOID AND ANTIPARATYPHOID B HORSE SERA WITH VARIOUS POLYSACCHARIDES

PubMed Central

Heidelberger, Michael; Cordoba, Felix

1956-01-01

A study was made of cross-reactions of synthetic polyglucose and of numerous plant and bacterial gums in an antityphoid and an antiparatyphoid B horse serum. The observed differences permit conclusions to be drawn regarding certain of the linkages likely to be found in the fine structures of each of the corresponding Salmonella polysaccharides:— 1. Cross-reactions of the antityphoid serum with the specific polysaccharide of Type II pneumococcus and with tamarind seed polysaccharide, glycogen and synthetic polyglucose indicate that the acetic acid-degraded O-polysaccharide of S. typhi, strain O 901, may contain part, at least, of its glucose as 1,4,6-branch points or in 1,6-linkage, perhaps adjacent to a terminal, non-reducing, galactopyranose unit. 2. Cross-reactions of both antisera with arabogalactans point to the existence of (probably β-) 1,3-, 1,6-, and/or 1,3,6-linkages of galactose in both the typhoid and paratyphoid B polysaccharides. 3. The differential reactivities of the galactomannans and yeast mannan suggest that the mannose in the typhoid polysaccharide is linked 1,2- or 1,3- with possible non-reducing mannopyranose end groups attached 1,6-. In the paratyphoid B polysaccharide the linkages are probably galacto-oligomannose 1,4-, or 1,4,6-, or the corresponding linkages of mannose alone. PMID:13357691

Microscopic haematuria: A rare presentation of typhoid fever.

PubMed

Nisahan, Balasingam; Thirunavukarasu, Kumanan; Selvaratnam, Gowry

2015-04-01

Typhoid fever can cause a number of renal manifestations heretofore dubbed 'nephrotyphoid'. Haematuria in the absence of renal impairment is extremely rare among typhoid patients. We report a case of an adult who presented with a prolonged febrile illness and microscopic haematuria. Blood culture confirmed the diagnosis of typhoid and the patient was treated successfully with ceftriaxone. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Vaccines for preventing typhoid fever.

PubMed

Milligan, Rachael; Paul, Mical; Richardson, Marty; Neuberger, Ami

2018-05-31

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages. To assess the effects of vaccines for preventing typhoid fever. In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible. Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses)A three-dose schedule of Ty21a vaccine probably prevents around half of typhoid cases during the first three years after vaccination (cumulative efficacy 2.5 to 3 years: 50%, 95% CI 35% to 61%, 4 trials, 235,239 participants, moderate-certainty evidence). These data include patients aged 3 to 44 years.Compared with placebo, this vaccine probably does not cause more vomiting, diarrhoea, nausea or abdominal pain (2 trials, 2066 participants; moderate-certainty evidence), headache, or rash (1 trial, 1190 participants; moderate-certainty evidence); however, fever (2 trials, 2066 participants; moderate-certainty evidence) is probably more common following vaccination.Vi polysaccharide vaccine (injection, one dose)A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (year 1: 69%, 95% CI 63% to 74%; 3 trials, 99,979 participants; high-certainty evidence). In year 2, trial results were more variable, with the vaccine probably preventing between 45% and 69% of typhoid cases (year 2: 59%, 95% CI 45% to 69%; 4 trials, 194,969 participants; moderate-certainty evidence). These data included participants aged 2 to 55 years of age.The three-year cumulative efficacy of the vaccine may be around 55% (95% CI 30% to 70%; 11,384 participants, 1 trial; low-certainty evidence). These data came from a single trial conducted in South Africa in the 1980s in participants aged 5 to 15 years.Compared with placebo, this vaccine probably did not increase the incidence of fever (3 trials, 132,261 participants; moderate-certainty evidence) or erythema (3 trials, 132,261 participants; low-certainty evidence); however, swelling (3 trials, 1767 participants; moderate-certainty evidence) and pain at the injection site (1 trial, 667 participants; moderate-certainty evidence) were more common in the vaccine group.Vi-rEPA vaccine (two doses)Administration of two doses of the Vi-rEPA vaccine probably prevents between 50% and 96% of typhoid cases during the first two years after vaccination (year 1: 94%, 95% CI 75% to 99%; year 2: 87%, 95% CI 56% to 96%, 1 trial, 12,008 participants; moderate-certainty evidence). These data came from a single trial with children two to five years of age conducted in Vietnam.Compared with placebo, both the first and the second dose of this vaccine increased the risk of fever (1 trial, 12,008 and 11,091 participants, low-certainty evidence) and the second dose increase the incidence of swelling at the injection site (one trial, 11,091 participants, moderate-certainty evidence).Vi-TT vaccine (two doses)We are uncertain of the efficacy of administration of two doses of Vi-TT (PedaTyph) in typhoid cases in children during the first year after vaccination (year 1: 94%, 95% CI -1% to 100%, 1 trial, 1625 participants; very low-certainty evidence). These data come from a single cluster-randomized trial in children aged six months to 12 years and conducted in India. For single dose Vi-TT (Typbar-TCV), we found no efficacy trials evaluating the vaccine with natural exposure.There were no reported serious adverse effects in RCTs of any of the vaccines studied. The licensed Ty21a and Vi polysaccharide vaccines are efficacious in adults and children older than two years in endemic countries. The Vi-rEPA vaccine is just as efficacious, although data is only available for children. The new Vi-TT vaccine (PedaTyph) requires further evaluation to determine if it provides protection against typhoid fever. At the time of writing, there were only efficacy data from a human challenge setting in adults on the Vi-TT vaccine (Tybar), which clearly justify the ongoing field trials to evaluate vaccine efficacy.

Genomic Signature of Multidrug-Resistant Salmonella enterica Serovar Typhi Isolates Related to a Massive Outbreak in Zambia between 2010 and 2012

PubMed Central

Leekitcharoenphon, Pimlapas; Lukjancenko, Oksana; Lukwesa-Musyani, Chileshe; Tambatamba, Bushimbwa; Mwaba, John; Kalonda, Annie; Nakazwe, Ruth; Kwenda, Geoffrey; Jensen, Jacob Dyring; Svendsen, Christina A.; Dittmann, Karen K.; Kaas, Rolf S.; Cavaco, Lina M.; Aarestrup, Frank M.; Hasman, Henrik; Mwansa, James C. L.

2014-01-01

Retrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole-genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the multilocus sequence type (MLST), haplotype, plasmid replicon, antimicrobial resistance genes, and genetic relatedness by single nucleotide polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients, with a fatality rate of 0.5%. Most (83.0%) isolates were multidrug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype, H58B. Most isolates contained a chromosomally translocated region containing seven antimicrobial resistance genes, catA1, blaTEM-1, dfrA7, sul1, sul2, strA, and strB, and fragments of the incompatibility group Q1 (IncQ1) plasmid replicon, the class 1 integron, and the mer operon. The genomic analysis revealed 415 SNP differences overall and 35 deletions among 33 of the isolates subjected to whole-genome sequencing. In comparison with other genomes of H58, the Zambian isolates separated from genomes from Central Africa and India by 34 and 52 SNPs, respectively. The phylogenetic analysis indicates that 32 of the 33 isolates sequenced belonged to a tight clonal group distinct from other H58 genomes included in the study. The small numbers of SNPs identified within this group are consistent with the short-term transmission that can be expected over a period of 2 years. The phylogenetic analysis and deletions suggest that a single MDR clone was responsible for the outbreak, during which occasional other S. Typhi lineages, including sensitive ones, continued to cocirculate. The common view is that the emerging global S. Typhi haplotype, H58B, containing the MDR IncHI1 plasmid is responsible for the majority of typhoid infections in Asia and sub-Saharan Africa; we found that a new variant of the haplotype harboring a chromosomally translocated region containing the MDR islands of IncHI1 plasmid has emerged in Zambia. This could change the perception of the term “classical MDR typhoid” currently being solely associated with the IncHI1 plasmid. It might be more common than presently thought that S. Typhi haplotype H58B harbors the IncHI1 plasmid or a chromosomally translocated MDR region or both. PMID:25392358

A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever

PubMed Central

Park, Ki Soo; Chung, Hyun Jung; Khanam, Farhana; Lee, Hakho; Rashu, Rasheduzzaman; Bhuiyan, Md. Taufiqur; Berger, Amanda; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.; Qadri, Firdausi; Weissleder, Ralph; Charles, Richelle C.

2016-01-01

There is currently no widely available optimal assay for diagnosing patients with enteric fever. Here we present a novel assay designed to detect amplified Salmonella nucleic acid (mRNA) using magneto-DNA probes and a miniaturized nuclear magnetic resonance device. We designed primers for genes specific to S. Typhi, S. Paratyphi A, and genes conserved among Salmonella enterica spp. and utilized strongly magnetized nanoparticles to enhance the detection signal. Blood samples spiked with in vitro grown S. Typhi, S. Paratyphi A, S. Typhimurium, and E. coli were used to confirm the specificity of each probe-set, and serial 10-fold dilutions were used to determine the limit of the detection of the assay, 0.01–1.0 CFU/ml. For proof of principle, we applied our assay to 0.5 mL blood samples from 5 patients with culture-confirmed enteric fever from Bangladesh in comparison to 3 healthy controls. We were able to detect amplified target cDNA in all 5 cases of enteric fever; no detectable signal was seen in the healthy controls. Our results suggest that a magneto-DNA nanoparticle system, with an assay time from blood collection of 3.5 hours, may be a promising platform for the rapid and culture-free diagnosis of enteric fever and non-typhoidal Salmonella bacteremia. PMID:27605393

Vaccines for preventing typhoid fever.

PubMed

Anwar, Elspeth; Goldberg, Elad; Fraser, Abigail; Acosta, Camilo J; Paul, Mical; Leibovici, Leonard

2014-01-02

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development. To evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever. In June 2013, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2013 and scanned the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease). Two review authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella typhi in blood. We calculated risk ratios (RRs) and efficacy (1-RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs were included in this review; 12 evaluated efficacy (Ty21a: five trials; Vi polysaccharide: six trials; Vi-rEPA: one trial), and 11 reported on adverse events. Ty21a vaccine (oral vaccine, three doses) A three-dose schedule of Ty21a vaccine prevents around one-third to one-half of typhoid cases in the first two years after vaccination (Year 1: 35%, 95% CI 8% to 54%; Year 2: 58%, 95% CI 40% to 71%; one trial, 20,543 participants; moderate quality evidence; data taken from a single trial conducted in Indonesia in the 1980s). No benefit was detected in the third year after vaccination. Four additional cluster-RCTs have been conducted, but the study authors did not adjust for clustering.Compared with placebo, this vaccine was not associated with more participants with vomiting, diarrhoea, nausea or abdominal pain (four trials, 2066 participants; moderate quality evidence) headache, or rash (two trials, 1190 participants; moderate quality evidence); however, fever (four trials, 2066 participants; moderate quality evidence) was more common in the vaccine group. Vi polysaccharide vaccine (injection, one dose) A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (Year 1: 69%, 95% CI 63% to 74%; three trials, 99,979 participants; high quality evidence). In Year 2, the trial results were more variable, with the vaccine preventing between 45% and 69% of typhoid cases (Year 2: 59%, 95% CI 45% to 69%; four trials, 194,969 participants; moderate quality evidence). The three-year cumulative efficacy of the vaccine is around 55% (95% CI 30% to 70%; 11,384 participants, one trial; moderate quality evidence). These data are taken from a single trial in South Africa in the 1980s.Compared with placebo, this vaccine was not associated with more participants with fever (four trials, 133,038 participants; moderate quality evidence) or erythema (three trials, 132,261 participants; low quality evidence); however, swelling (three trials, 1767 participants; moderate quality evidence) and pain at the injection site (one trial, 667 participants; moderate quality evidence) were more common in the vaccine group. Vi-rEPA vaccine (two doses) Administration of two doses of the Vi-rEPA vaccine prevents between 50% and 96% of typhoid cases during the first two years after vaccination (Year 1: 94%, 95% CI 75% to 99%; Year 2: 87%, 95% CI 56% to 96%; one trial, 12,008 participants; moderate quality evidence). These data are taken from a single trial with children 2 to 5 years of age conducted in Vietnam.Compared with placebo, the first and second doses of this vaccine were not associated with increased risk of adverse events. The first dose of this vaccine was not associated with fever (2 studies, 12,209 participants; low quality evidence), erythema (two trials, 12,209 participants; moderate quality evidence) or swelling at the injection site (two trials, 12,209 participants; moderate quality evidence). The second dose of this vaccine was not associated with fever (two trials, 11,286 participants; low quality evidence), erythema (two trials, 11,286 participants; moderate quality evidence) and swelling at the injection site (two trials, 11,286 participants; moderate quality evidence). The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.

Comparative evaluation of two Rickettsia typhi-specific quantitative real-time PCRs for research and diagnostic purposes.

PubMed

Papp, Stefanie; Rauch, Jessica; Kuehl, Svenja; Richardt, Ulricke; Keller, Christian; Osterloh, Anke

2017-02-01

Rickettsioses are caused by intracellular bacteria of the family of Rickettsiaceae. Rickettsia (R.) typhi is the causative agent of endemic typhus. The disease occurs worldwide and is one of the most prevalent rickettsioses. Rickettsial diseases, however, are generally underdiagnosed which is mainly due to the lack of sensitive and specific methods. In addition, methods for quantitative detection of the bacteria for research purposes are rare. We established two qPCRs for the detection of R. typhi by amplification of the outer membrane protein B (ompB) and parvulin-type PPIase (prsA) genes. Both qPCRs are specific and exclusively recognize R. typhi but no other rickettsiae including the closest relative, R. prowazekii. The prsA-based qPCR revealed to be much more sensitive than the amplification of ompB and provided highly reproducible results in the detection of R. typhi in organs of infected mice. Furthermore, as a nested PCR the prsA qPCR was applicable for the detection of R. typhi in human blood samples. Collectively, the prsA-based qPCR represents a reliable method for the quantitative detection of R. typhi for research purposes and is a promising candidate for differential diagnosis.

Formative Investigation of Acceptability of Typhoid Vaccine during a Typhoid Fever Outbreak in Neno District, Malawi

PubMed Central

Blum, Lauren S.; Dentz, Holly; Chingoli, Felix; Chilima, Benson; Warne, Thomas; Lee, Carla; Hyde, Terri; Gindler, Jacqueline; Sejvar, James; Mintz, Eric D.

2014-01-01

Typhoid fever affects an estimated 22 million people annually and causes 216,000 deaths worldwide. We conducted an investigation in August and September 2010 to examine the acceptability of typhoid vaccine in Neno District, Malawi where a typhoid outbreak was ongoing. We used qualitative methods, including freelisting exercises, key informant and in-depth interviews, and group discussions. Respondents associated illness with exposure to “bad wind,” and transmission was believed to be airborne. Typhoid was considered extremely dangerous because of its rapid spread, the debilitating conditions it produced, the number of related fatalities, and the perception that it was highly contagious. Respondents were skeptical about the effectiveness of water, sanitation, and hygiene (WaSH) interventions. The perceived severity of typhoid and fear of exposure, uncertainty about the effectiveness of WaSH measures, and widespread belief in the efficacy of vaccines in preventing disease resulted in an overwhelming interest in receiving typhoid vaccine during an outbreak. PMID:25002303

Formative investigation of acceptability of typhoid vaccine during a typhoid fever outbreak in Neno District, Malawi.

PubMed

Blum, Lauren S; Dentz, Holly; Chingoli, Felix; Chilima, Benson; Warne, Thomas; Lee, Carla; Hyde, Terri; Gindler, Jacqueline; Sejvar, James; Mintz, Eric D

2014-10-01

Typhoid fever affects an estimated 22 million people annually and causes 216,000 deaths worldwide. We conducted an investigation in August and September 2010 to examine the acceptability of typhoid vaccine in Neno District, Malawi where a typhoid outbreak was ongoing. We used qualitative methods, including freelisting exercises, key informant and in-depth interviews, and group discussions. Respondents associated illness with exposure to "bad wind," and transmission was believed to be airborne. Typhoid was considered extremely dangerous because of its rapid spread, the debilitating conditions it produced, the number of related fatalities, and the perception that it was highly contagious. Respondents were skeptical about the effectiveness of water, sanitation, and hygiene (WaSH) interventions. The perceived severity of typhoid and fear of exposure, uncertainty about the effectiveness of WaSH measures, and widespread belief in the efficacy of vaccines in preventing disease resulted in an overwhelming interest in receiving typhoid vaccine during an outbreak. © The American Society of Tropical Medicine and Hygiene.

Non-protein coding RNA genes as the novel diagnostic markers for the discrimination of Salmonella species using PCR.

PubMed

Nithya, Ravichantar; Ahmed, Siti Aminah; Hoe, Chee-Hock; Gopinath, Subash C B; Citartan, Marimuthu; Chinni, Suresh V; Lee, Li Pin; Rozhdestvensky, Timofey S; Tang, Thean-Hock

2015-01-01

Salmonellosis, a communicable disease caused by members of the Salmonella species, transmitted to humans through contaminated food or water. It is of paramount importance, to generate accurate detection methods for discriminating the various Salmonella species that cause severe infection in humans, including S. Typhi and S. Paratyphi A. Here, we formulated a strategy of detection and differentiation of salmonellosis by a multiplex polymerase chain reaction assay using S. Typhi non-protein coding RNA (sRNA) genes. With the designed sequences that specifically detect sRNA genes from S. Typhi and S. Paratyphi A, a detection limit of up to 10 pg was achieved. Moreover, in a stool-seeding experiment with S. Typhi and S. Paratyphi A, we have attained a respective detection limit of 15 and 1.5 CFU/mL. The designed strategy using sRNA genes shown here is comparatively sensitive and specific, suitable for clinical diagnosis and disease surveillance, and sRNAs represent an excellent molecular target for infectious disease.

Structural and Network-based Methods for Knowledge-Based Systems

DTIC Science & Technology

2011-12-01

depth) provide important information about knowledge gaps in the KB. For example, if SuccessEstimate (causes-EventEvent, Typhoid - Fever , 1, 3) is...equal to 0, it points toward lack of biological knowledge about Typhoid - Fever in our KB. Similar information can also be obtained from the...position of the consequent. ⋃ ( ( ) ) Therefore, if Q does not contain Typhoid - Fever , then obtaining

[A classical but unknown cause of peritoneal effusion disclosed by echography. Typhoid fever].

PubMed

Judet, O; Rouveix, E; Verderi, D; Bismuth, V

1989-01-01

Two cases of peritoneal effusion discovered by sonography in patients with typhoid fever are reported. These peritoneal effusions have no pejorative value; only clinical findings can differentiate these simple effusions from a perforative thyphoid peritonitis, which is exceptional nowadays. Typhoid fever, among other febrile diseases should be considered when ultrasounds shows an isolated peritoneal effusion.

Etiology of Acute, Non-Malaria, Febrile Illnesses in Jayapura, Northeastern Papua, Indonesia

PubMed Central

Punjabi, Narain H.; Taylor, Walter R. J.; Murphy, Gerald S.; Purwaningsih, Sri; Picarima, Helena; Sisson, John; Olson, James G.; Baso, Samuel; Wangsasaputra, Ferry; Lesmana, Murad; Oyofo, Buhari A.; Simanjuntak, Cyrus H.; Subekti, Decy; Corwin, Andrew L.; Richie, Thomas L.

2012-01-01

We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997–2000, 226 patients (127 males and 99 females) 1–80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had ≥ 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli–positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics. PMID:22232450

Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers.

PubMed

Roggelin, Louise; Vinnemeier, Christof D; Fischer-Herr, Johanna; Johnson-Weaver, Brandi T; Rolling, Thierry; Burchard, Gerd D; Staats, Herman F; Cramer, Jakob P

2015-08-07

An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines. In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix(®) (GlaxoSmithKline), Typhim Vi(®) (Sanofi Pasteur MSD) or Hepatyrix(®) (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (-1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA. Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40 μg/ml versus 6.13 μg/ml, P=0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34 μg/ml versus 14.58 μg/ml, P=0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0. In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular evidence of Rickettsia typhi infection in dogs from a rural community in Yucatán, México.

PubMed

Martínez-Ortiz, Daly; Torres-Castro, Marco; Koyoc-Cardeña, Edgar; López, Karina; Panti-May, Alonso; Rodríguez-Vivas, Iván; Puc, Adriano; Dzul, Karla; Zavala-Castro, Jorge; Medina-Barreiro, Anuar; Chablé-Santos, Juan; Manrique-Saide, Pablo

2016-02-23

Rickettsia typhi causes murine or endemic typhus, which is transmitted to humans primarily through flea bites contaminated with feces. Synanthropic and domestic animals also contribute to the infection cycle of R. typhi. Cases of murine typhus in humans were reported in the rural community of Bolmay, Yucatán, México, between 2007 and 2010.  To identify the presence of R. typhi and estimate the frequency of infection in dogs from Bolmay, México, a locality with previous reports of murine typhus in humans.  Whole blood samples were taken from 128 dogs. Total DNA was extracted for use in the polymerase chain reaction (PCR) to amplify fragments of the 17 kDa and omp B genes and confirms the presence of Rickettsia spp. The reaction products were sequenced, and alignment analysis was performed using the BLAST tool.  The frequency of R. typhi infection in dogs was 5.5 % (7/128). The alignment identified 99% and 100% homology to the R. typhi 17 kDa and omp B genes, respectively.  We confirmed the presence of R. typhi in dogs in the studied community but at a low frequency. However, there is potential risk of transmission to humans.

Arthritis in ducks. I. Aetiology and public health aspects.

PubMed

Bisgaard, M

1981-01-01

A pure culture of potentially pathogenic bacteria was obtained from 90% of 233 joints examined, originating from 232 ducks condemned due to arthritis at slaughter. S. typhi-murium and Staph. aureus were isolated from 61% and 18% of the joints respectively. E. coli was obtained from 6% of the cases, serogroup 078 being most prevalent. E. rhusiopathiae, Y. pseudo-tuberculosis, P. vulgaris, Micrococcus sp., Streptococcus sp., Acinetobacter sp., Flavobacterium sp., Pseudomonas sp. and Ae. formicans made up 12 cases. Serotypes other than S. typhi-murium were prevalent among ducks from all farms investigated, but S. typhi-murium was the only serotype demonstrated in arthritis. A high incidence of S. typhi-murium in the intestinal tract of ducks maintained on free range or in open houses suggests that these sites are sources of infection and that the intestinal tract is the portal of entry for S. typhi-murium causing arthritis. Ducks with arthritis at slaughter should always be totally condemned because of the public health hazard from the organisms most often associated with this condition.

The clinical and microbiological characteristics of enteric fever in Cambodia, 2008-2015

PubMed Central

Phe, Thong; Veng, Chhun H.; Lim, Kruy; Ieng, Sovann; Kham, Chun; Fawal, Nizar; Fabre, Laetitia; Le Hello, Simon; Vlieghe, Erika; Weill, François-Xavier; Jacobs, Jan; Peetermans, Willy E.

2017-01-01

Background Enteric fever remains a major public health problem in low resource settings and antibiotic resistance is increasing. In Asia, an increasing proportion of infections is caused by Salmonella enterica serovar Paratyphi A, which for a long time was assumed to cause a milder clinical syndrome compared to Salmonella enterica serovar Typhi. Methodology A retrospective chart review study was conducted of 254 unique cases of blood culture confirmed enteric fever who presented at a referral adult hospital in Phnom Penh, Cambodia between 2008 and 2015. Demographic, clinical and laboratory data were collected from clinical charts and antibiotic susceptibility testing was performed. Whole genome sequence analysis was performed on a subset of 121 isolates. Results One-hundred-and-ninety unique patients were diagnosed with Salmonella Paratyphi A and 64 with Salmonella Typhi. In the period 2008–2012, Salmonella Paratyphi A comprised 25.5% of 47 enteric fever cases compared to 86.0% of 207 cases during 2013–2015. Presenting symptoms were identical for both serovars but higher median leukocyte counts (6.8 x 109/L vs. 6.3 x 109/L; p = 0.035) and C-reactive protein (CRP) values (47.0 mg/L vs. 36 mg/L; p = 0.034) were observed for Salmonella Typhi infections. All but one of the Salmonella Typhi isolates belonged to haplotype H58 associated with multidrug resistance (MDR) (i.e. resistance to ampicillin, chloramphenicol and co-trimoxazole).;42.9% actually displayed MDR compared to none of the Salmonella Paratyphi A isolates. Decreased ciprofloxacin susceptibility (DCS) was observed in 96.9% (62/64) of Salmonella Typhi isolates versus 11.5% (21/183) of Salmonella Paratyphi A isolates (all but one from 2015). All isolates were susceptible to azithromycin and ceftriaxone. Conclusions In Phnom Penh, Cambodia, Salmonella Paratyphi A now causes the majority of enteric fever cases and decreased susceptibility against ciprofloxacin is increasing. Overall, Salmonella Typhi was significantly more associated with MDR and DCS compared to Salmonella Paratyphi A. PMID:28931025

The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi

PubMed Central

Arcuri, M.; Di Benedetto, R.; Cunningham, A. F.; Saul, A.; MacLennan, C. A.

2017-01-01

In recent years there have been major efforts to develop glycoconjugate vaccines based on the Vi polysaccharide that will protect against Salmonella enterica Typhi infections, particularly typhoid fever, which remains a major public health concern in low-income countries. The design of glycoconjugate vaccines influences the immune responses they elicit. Here we systematically test the response in mice to Vi glycoconjugates that differ in Vi chain length (full-length and fragmented), carrier protein, conjugation chemistry, saccharide to protein ratio and size. We show that the length of Vi chains, but not the ultimate size of the conjugate, has an impact on the anti-Vi IgG immune response induced. Full-length Vi conjugates, independent of the carrier protein, induce peak IgG responses rapidly after just one immunization, and secondary immunization does not enhance the magnitude of these responses. Fragmented Vi linked to CRM197 and diphtheria toxoid, but not to tetanus toxoid, gives lower anti-Vi antibody responses after the first immunization than full-length Vi conjugates, but antibody titres are similar to those induced by full-length Vi conjugates following a second dose. The chemistry to conjugate Vi to the carrier protein, the linker used, and the saccharide to protein ratio do not significantly alter the response. We conclude that Vi length and carrier protein are the variables that influence the anti-Vi IgG response to immunization the most, while other parameters are of lesser importance. PMID:29287062

Anti-Salmonella activity of medicinal plants from Cameroon.

PubMed

Nkuo-Akenji, T; Ndip, R; McThomas, A; Fru, E C

2001-06-01

To evaluate the effects of herbal extracts derived from plants commonly prescribed by traditional practitioners for the treatment of typhoid fever. A cross sectional study. Departments of Life Sciences and Chemistry, University of Buea, Cameroon. Methanol extracts of plant parts commonly used in Cameroon for the treatment of typhoid fever. Antimicrobial activity was tested using the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) assays. Methanol extracts of plant parts commonly used in Cameroon for the treatment of typhoid fever were tested for antibacterial activity against Salmonella typhi, S. paratyphi and S. typhimurium. The formulations used were: 1) Formulation A comprising Cymbogogon citratus leaves, Carica papaya leaves, and Zea mays silk. 2) Formulation B comprising C. papaya roots, Mangifera indica leaves, Citrus limon fruit and C. citratus leaves. 3) C. papaya leaves. 4) Emilia coccinea whole plant. 5) Comelina bengalensis leaves. 6) Telfaria occidentalis leaves. 7) Gossypium arboreum whole plant. Antimicrobial activity was tested using the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) assays. Generally, Formulation A elicited inhibitory activity at a lower range of 0.02 to 0.06 mg/ml. Similarly, Formulation B elicited bacterial activity at the lowest range of 0.06 to 0.25 mg/ml. C. bengalensis leaves on the other hand, showed the lowest activity with a concentration range of 0.132 to 2.0 mg/ml and 1 to 4 mg/ml in MIC and MBC assays respectively. S. paratyphi was most sensitive to the formulations (concentration range of 0.02 to 1 mg/ml in both MIC and MBC assays) while S. typhimurium was the least sensitive and concentrations of up to 4 mg/ml were required to be bactericidal. It is concluded that plant extracts with low MIC and MBC values (1 mg/ml and lower) may contain compounds with therapeutic activity.

An experimental model of human body louse infection with Rickettsia typhi.

PubMed

Houhamdi, Linda; Fournier, Pierre-Edouard; Fang, Rong; Raoult, Didier

2003-06-01

Murine (endemic) typhus caused by Rickettsia typhi, one of the most widely distributed arthropod-borne diseases, is transmitted to humans mainly by the oriental rat flea. The human body louse, Pediculus humanus corporis, has been suspected to have a role in the transmission of R. typhi to humans. To evaluate the potential role of Pediculus humanus corporis as a vector of murine typhus, we used R. typhi in an experimental model of human body louse infection previously used with R. prowazekii. A rabbit was made bacteremic by inoculating it with 2 x 10(6) plaque-forming units of R. typhi; it remained bacteremic for at least 59 hours. Two hundred body lice infected by feeding on the bacteremic rabbit were compared to 200 uninfected control lice. Each louse population was fed once a day on the abdomen of a seronegative rabbit. On day 8 post-infection, as a result of disruption of the gut cells and leakage of the blood meal into the hemolymph, four infected lice became bright red and died within four hours. The life span of infected lice was 20 days less than that of the controls. Infected lice did not transmit R. typhi to their progeny (eggs and larvae) as demonstrated by PCR amplification and cell culture. With an immunofluorescence assay, R. typhi was detected in feces from day 7 post-infection, and the organism remained viable in feces for up to 80 days as demonstrated by cell culture. From the 21st day post-infection, the rabbit used to feed the R. typhi-infected lice developed an immunoglobulin response with a titer of 1:50 increasing to 1:200 at the 42nd day post-infection. It showed no clinical signs of infection. The rabbit that was used to feed uninfected lice remained seronegative. Although body lice are not clearly identified vectors of R. typhi, it seems that under certain circumstances they could transmit R. typhi.

Occurrence of ß-lactamase genes among non-Typhi Salmonella enterica isolated from humans, food animals, and retail meats in the United States and Canada

USDA-ARS?s Scientific Manuscript database

Non-Typhi Salmonella cause over 1.7 million cases of gastroenteritis in North America each year, and food-animal products are commonly implicated in human infections. For invasive infections, antimicrobial therapy is implicated. In North America, the antimicrobial susceptibility of Salmonella is m...

Levofloxacin in enteric fever--a study.

PubMed

Kadam, G S; Naikwadi, Akram; Rao, S K Srinivasa; Sawardekar, Suresh S; Gawde, Ashish; Baliga, Vidyagauri; Desai, Anish

2005-08-01

Typhoid fever is an important cause of morbidity and mortality in patients especially in developing country. Therapy with conventional drugs is associated with increasing resistance, non-compliance to therapy and toxicity. Oral fluoroquinolones have been shown to be effective compared to parenteral broad-spectrum cephalosporins in the treatment of uncomplicated typhoid. However, there is no data available regarding the use of levofloxacin in the treatment of typhoid fever in spite of the susceptibility of Salmonella species to levofloxacin. The present study was undertaken to evaluate the efficacy, safety and tolerability of oral levofloxacin 750 mg once daily in the treatment of typhoid fever. Results indicated that levofloxacin 750 mg administered orally once daily was an effective, safe, well-tolerated and cost-effective option in the treatment of typhoid fever in adult Indian males and non-pregnant females.

Evolutionary genetic relationships of clones of Salmonella serovars that cause human typhoid and other enteric fevers.

PubMed Central

Selander, R K; Beltran, P; Smith, N H; Helmuth, R; Rubin, F A; Kopecko, D J; Ferris, K; Tall, B D; Cravioto, A; Musser, J M

1990-01-01

Multilocus enzyme electrophoresis was employed to measure chromosomal genotypic diversity and evolutionary relationships among 761 isolates of the serovars Salmonella typhi, S. paratyphi A, S. paratyphi B, S. paratyphi C, and S. sendai, which are human-adapted agents of enteric fever, and S. miami and S. java, which are serotypically similar to S. sendai and S. paratyphi B, respectively, but cause gastroenteritis in both humans and animals. To determine the phylogenetic positions of the clones of these forms within the context of the salmonellae of subspecies I, comparative data for 22 other common serovars were utilized. Except for S. paratyphi A and S. sendai, the analysis revealed no close phylogenetic relationships among clones of different human-adapted serovars, which implies convergence in host adaptation and virulence factors. Clones of S. miami are not allied with those of S. sendai or S. paratyphi A, being, instead, closely related to strains of S. panama. Clones of S. paratyphi B and S. java belong to a large phylogenetic complex that includes clones of S. typhimurium, S. heidelberg, S. saintpaul, and S. muenchen. Most strains of S. paratyphi B belong to a globally distributed clone that is highly polymorphic in biotype, bacteriophage type, and several other characters, whereas strains of S. java represent seven diverse lineages. The flagellar monophasic forms of S. java are genotypically more similar to clones of S. typhimurium than to other clones of S. java or S. paratyphi B. Clones of S. paratyphi C are related to those of S. choleraesuis. DNA probing with a segment of the viaB region specific for the Vi capsular antigen genes indicated that the frequent failure of isolates of S. paratyphi C to express Vi antigen is almost entirely attributable to regulatory processes rather than to an absence of the structural determinant genes themselves. Two clones of S. typhisuis are related to those of S. choleraesuis and S. paratyphi C, but a third clone is not. Although the clones of S. decatur and S. choleraesuis are serologically and biochemically similar, they are genotypically very distinct. Two clones of S. typhi were distinguished, one globally distributed and another apparently confined to Africa; both clones are distantly related to those of all other serovars studied. Images PMID:1973153

Bacteria and cancer: cause, coincidence or cure? A review

PubMed Central

Mager, DL

2006-01-01

Research has found that certain bacteria are associated with human cancers. Their role, however, is still unclear. Convincing evidence links some species to carcinogenesis while others appear promising in the diagnosis, prevention or treatment of cancers. The complex relationship between bacteria and humans is demonstrated by Helicobacter pylori and Salmonella typhi infections. Research has shown that H. pylori can cause gastric cancer or MALT lymphoma in some individuals. In contrast, exposure to H. pylori appears to reduce the risk of esophageal cancer in others. Salmonella typhi infection has been associated with the development of gallbladder cancer; however S. typhi is a promising carrier of therapeutic agents for melanoma, colon and bladder cancers. Thus bacterial species and their roles in particular cancers appear to differ among different individuals. Many species, however, share an important characteristic: highly site-specific colonization. This critical factor may lead to the development of non-invasive diagnostic tests, innovative treatments and cancer vaccines. PMID:16566840

Dengue hemorrhagic fever and typhoid fever association based on spatial standpoint using scan statistics in DKI Jakarta

NASA Astrophysics Data System (ADS)

Hervind, Widyaningsih, Y.

2017-07-01

Concurrent infection with multiple infectious agents may occur in one patient, it appears frequently in dengue hemorrhagic fever (DHF) and typhoid fever. This paper depicted association between DHF and typhoid based on spatial point of view. Since paucity of data regarding dengue and typhoid co-infection, data that be used are the number of patients of those diseases in every district (kecamatan) in Jakarta in 2014 and 2015 obtained from Jakarta surveillance website. Poisson spatial scan statistics is used to detect DHF and typhoid hotspots area district in Jakarta separately. After obtain the hotspot, Fisher's exact test is applied to validate association between those two diseases' hotspot. The result exhibit hotspots of DHF and typhoid are located around central Jakarta. The further analysis used Poisson space-time scan statistics to reveal the hotspot in term of spatial and time. DHF and typhoid fever more likely occurr from January until May in the area which is relatively similar with pure spatial result. Preventive action could be done especially in the hotspot areas and it is required further study to observe the causes based on characteristics of the hotspot area.

Typhoid fever in Fiji: a reversible plague?

PubMed

Thompson, Corinne N; Kama, Mike; Acharya, Shrish; Bera, Una; Clemens, John; Crump, John A; Dawainavesi, Aggie; Dougan, Gordon; Edmunds, W John; Fox, Kimberley; Jenkins, Kylie; Khan, M Imran; Koroivueta, Josefa; Levine, Myron M; Martin, Laura B; Nilles, Eric; Pitzer, Virginia E; Singh, Shalini; Raiwalu, Ratu Vereniki; Baker, Stephen; Mulholland, Kim

2014-10-01

The country of Fiji, with a population of approximately 870 000 people, faces a growing burden of several communicable diseases including the bacterial infection typhoid fever. Surveillance data suggest that typhoid has become increasingly common in rural areas of Fiji and is more frequent amongst young adults. Transmission of the organisms that cause typhoid is facilitated by faecal contamination of food or water and may be influenced by local behavioural practices in Fiji. The Fijian Ministry of Health, with support from Australian Aid, hosted a meeting in August 2012 to develop comprehensive control and prevention strategies for typhoid fever in Fiji. International and local specialists were invited to share relevant data and discuss typhoid control options. The resultant recommendations focused on generating a clearer sense of the epidemiology of typhoid in Fiji and exploring the contribution of potential transmission pathways. Additionally, the panel suggested steps such as ensuring that recommended ciprofloxacin doses are appropriate to reduce the potential for relapse and reinfection in clinical cases, encouraging proper hand hygiene of food and drink handlers, working with water and sanitation agencies to review current sanitation practices and considering a vaccination policy targeting epidemiologically relevant populations. © 2014 The Authors. Tropical Medicine & International Health published by John Wiley & Sons Ltd.

Vaccination for typhoid fever in sub-Saharan Africa.

PubMed

Slayton, Rachel B; Date, Kashmira A; Mintz, Eric D

2013-04-01

Emerging data on the epidemiologic, clinical and microbiologic aspects of typhoid fever in sub-Saharan Africa call for new strategies and new resources to bring the regional epidemic under control. Areas with endemic disease at rates approaching those in south Asia have been identified; large, prolonged and severe outbreaks are occurring more frequently; and resistance to antimicrobial agents, including fluoroquinolones is increasing. Surveillance for typhoid fever is hampered by the lack of laboratory resources for rapid diagnosis, culture confirmation and antimicrobial susceptibility testing. Nonetheless, in 2010, typhoid fever was estimated to cause 725 incident cases and 7 deaths per 100,000 person years in sub-Saharan Africa. Efforts for prevention and outbreak control are challenged by limited access to safe drinking water and sanitation and by a lack of resources to initiate typhoid immunization. A comprehensive approach to typhoid fever prevention including laboratory and epidemiologic capacity building, investments in water, sanitation and hygiene and reconsideration of the role of currently available vaccines could significantly reduce the disease burden. Targeted vaccination using currently available typhoid vaccines should be considered as a short- to intermediate-term risk reduction strategy for high-risk groups across sub-Saharan Africa.

Typhoid fever in Fiji: a reversible plague?

PubMed Central

Thompson, Corinne N; Kama, Mike; Acharya, Shrish; Bera, Una; Clemens, John; Crump, John A; Dawainavesi, Aggie; Dougan, Gordon; Edmunds, W John; Fox, Kimberley; Jenkins, Kylie; Khan, M Imran; Koroivueta, Josefa; Levine, Myron M; Martin, Laura B; Nilles, Eric; Pitzer, Virginia E; Singh, Shalini; Raiwalu, Ratu Vereniki; Baker, Stephen; Mulholland, Kim

2014-01-01

The country of Fiji, with a population of approximately 870 000 people, faces a growing burden of several communicable diseases including the bacterial infection typhoid fever. Surveillance data suggest that typhoid has become increasingly common in rural areas of Fiji and is more frequent amongst young adults. Transmission of the organisms that cause typhoid is facilitated by faecal contamination of food or water and may be influenced by local behavioural practices in Fiji. The Fijian Ministry of Health, with support from Australian Aid, hosted a meeting in August 2012 to develop comprehensive control and prevention strategies for typhoid fever in Fiji. International and local specialists were invited to share relevant data and discuss typhoid control options. The resultant recommendations focused on generating a clearer sense of the epidemiology of typhoid in Fiji and exploring the contribution of potential transmission pathways. Additionally, the panel suggested steps such as ensuring that recommended ciprofloxacin doses are appropriate to reduce the potential for relapse and reinfection in clinical cases, encouraging proper hand hygiene of food and drink handlers, working with water and sanitation agencies to review current sanitation practices and considering a vaccination policy targeting epidemiologically relevant populations. PMID:25066005

Clinical and Epidemiological Characteristics of Scrub Typhus and Murine Typhus among Hospitalized Patients with Acute Undifferentiated Fever in Northern Vietnam

PubMed Central

Hamaguchi, Sugihiro; Cuong, Ngo Chi; Tra, Doan Thu; Doan, Yen Hai; Shimizu, Kenta; Tuan, Nguyen Quang; Yoshida, Lay-Myint; Mai, Le Quynh; Duc-Anh, Dang; Ando, Shuji; Arikawa, Jiro; Parry, Christopher M.; Ariyoshi, Koya; Thuy, Pham Thanh

2015-01-01

A descriptive study on rickettsiosis was conducted at the largest referral hospital in Hanoi, Vietnam, to identify epidemiological and clinical characteristics of specific rickettsiosis. Between March 2001 and February 2003, we enrolled 579 patients with acute undifferentiated fever (AUF), excluding patients with malaria, dengue fever, and typhoid fever, and serologically tested for Orientia tsutsugamushi and Rickettsia typhi. Of the patients, 237 (40.9%) and 193 (33.3%) had scrub and murine typhus, respectively, and 149 (25.7%) had neither of them (non–scrub and murine typhus [non-ST/MT]). The proportion of murine typhus was highest among patients living in Hanoi whereas that of scrub typhus was highest in national or regional border areas. The presence of an eschar, dyspnea, hypotension, and lymphadenopathy was significantly associated with a diagnosis of scrub typhus (OR = 46.56, 10.90, 9.01, and 7.92, respectively). Patients with murine typhus were less likely to have these findings but more likely to have myalgia, rash, and relative bradycardia (OR = 1.60, 1.56, and 1.45, respectively). Scrub typhus and murine typhus were shown to be common causes of AUF in northern Vietnam although the occurrence of spotted fever group rickettsiae was not determined. Clinical and epidemiological information may help local clinicians make clinical diagnosis of specific rickettsioses in a resource-limited setting. PMID:25778504

Typhoid vaccine: a case for inclusion in national program.

PubMed

Sharma, Pragya; Taneja, Davendra K

2011-01-01

Typhoid has been reported to be a common and significant cause of morbidity in pre-school and school-age children in the endemic countries like India. The incidence of typhoid has been reported to be as high as 27.3 per 1000 person-years in children less than 5 years of age. Serious complications occur in about 10% of cases requiring hospitalization. The mean cost of treatment per episode of blood culture-confirmed typhoid fever has been calculated as INR 3,597 (1996 prices) in an outdoor setting, whereas in case of hospitalization, the cost of illness increases by several folds (INR 18,131). Vi polysaccharide vaccine is safe, efficacious and affordable for use as a cost-effective public health tool to protect children from typhoid and related complications, when given at 2 and 5 years of age as a part of National Immunization Schedule.

Enteric Fever in Children in Western Sydney, Australia, 2003-2015.

PubMed

Khatami, Ameneh; Khan, Fouzia; Macartney, Kristine K

2017-12-01

Enteric fever is a vaccine-preventable disease with cases in Australia predominantly acquired overseas. The aim of this study was to define the burden of enteric fever in children presenting to a pediatric hospital in Western Sydney between 2003 and 2015. Cases between January 2003 and December 2013 were ascertained through medical records using International Classification of Disease-coded discharge diagnoses, cross-referenced with microbiology laboratory data for all isolates of Salmonella enterica serovar typhi and S. enterica serovar paratyphi. Prospective cases from January 2014 to April 2015 were additionally captured through records maintained by the infectious diseases team. Seventy-one cases of enteric fever were identified in 12.3 years with an average of 4 cases per year between 2003 and 2008 and 7 cases per year between 2009 and 2014. Two were visitors to Australia, 8 were recent migrants, and 59 were Australian residents returning from overseas travel. Two children had no history of overseas travel. Countries of travel predominantly included the Indian subcontinent (60/69) and Southeast Asia (7/69). Of 30 children with information available on pretravel medical consultation, 1 was offered and received typhoid vaccine. Ninety-four percent of children (67) required admission for 1-28 days (median: 5 days). Three children required readmission, with 1 case of presumed relapse. Ninety percent (64) were diagnosed by blood or stool culture with S. enterica serovar typhi the predominant organism (54/64). In Australia, hospitalizations for pediatric enteric fever appear to be increasing; predominantly occurring in Australian-resident children. Greater awareness and education are required for parents and clinicians regarding travel health risks and prevention strategies.

Impact of a Targeted Typhoid Vaccination Campaign Following Cyclone Tomas, Republic of Fiji, 2010

PubMed Central

Scobie, Heather M.; Nilles, Eric; Kama, Mike; Kool, Jacob L.; Mintz, Eric; Wannemuehler, Kathleen A.; Hyde, Terri B.; Dawainavesi, Akanisi; Singh, Sheetalpreet; Korovou, Samuel; Jenkins, Kylie; Date, Kashmira

2014-01-01

After a category 4 cyclone that caused extensive population displacement and damage to water and sanitation infrastructure in Fiji in March 2010, a typhoid vaccination campaign was conducted as part of the post-disaster response. During June–December 2010, 64,015 doses of typhoid Vi polysaccharide vaccine were administered to persons ≥ 2 years of age, primarily in cyclone-affected areas that were typhoid endemic. Annual typhoid fever incidence decreased during the post-campaign year (2011) relative to preceding years (2008–2009) in three subdivisions where a large proportion of the population was vaccinated (incidence rate ratios and 95% confidence intervals: 0.23, 0.13–0.41; 0.24, 0.14–0.41; 0.58, 0.40–0.86), and increased or remained unchanged in 12 subdivisions where little to no vaccination occurred. Vaccination played a role in reducing typhoid fever incidence in high-incidence areas after a disaster and should be considered in endemic settings, along with comprehensive control measures, as recommended by the World Health Organization. PMID:24710618

Rickettsia Felis in Xenopsylla Cheopis, Java, Indonesia

DTIC Science & Technology

2006-08-01

Sardjono TW, Yanuwiadi B, Hernowati TE, et al. Seroepidemiological evidence for murine and scrub typhus in Malang, Indonesia. Am J Trop Med Hyg. 1997;57...and Allen L. Richards* Rickettsia typhi and R. felis, etiologic agents of murine typhus and fleaborne spotted fever, respectively, were detected in...Indonesia and nat- urally occurring R. felis in Oriental rat fleas. Murine typhus (endemic typhus , fleaborne typhus ),caused by Rickettsia typhi, is

Diversity of Salmonella enterica serovar Typhi strains collected from india using variable number tandem repeat (VNTR)-PCR analysis.

PubMed

Sankar, Sathish; Kuppanan, Suresh; Nandagopal, Balaji; Sridharan, Gopalan

2013-08-01

Typhoid fever is endemic in India, and a seasonal increase of cases is observed annually. In spite of effective therapies and the availability of vaccines, morbidity is widespread owing to the circulation of multiple genetic variants, frequent migration of asymptomatic carriers, unhygienic food practices and the emergence of multidrug resistance and thus continues to be a major public health problem in developing countries, particularly in India. Classical methods of strain typing such as pulsed-field gel electrophoresis, ribotyping, random amplification of polymorphic DNA and amplified fragment length polymorphism are either laborious and technically complicated or less discriminatory. We investigated the molecular diversity of Indian strains of Salmonella enterica serovar Typhi (S. Typhi) isolated from humans from different parts of India to establish the molecular epidemiology of the organism using the variable number tandem repeat (VNTR)-PCR analysis. The electrophoretic band pattern was analysed using the GelCompar II software program. Of the 94 strains tested for three VNTRs loci, 75 VNTR genotypes were obtained. Of the three VNTRs tested in this study, VNTR1 was amplified in all the strains except one and found to be predominant. VNTR2 was amplified only in 57 strains with a Simpson diversity index of 0.93 indicating the high variability of this region within the strains. VNTR3 was amplified in 90 strains. The discriminatory power of this typing tool has been greatly enhanced by this VNTR2 region as the other two regions could not discriminate strains significantly. In our study, about 55 % of the strains amplified all three VNTR regions and 39 % of the strains lacked the VNTR2 region. Among the three VNTR regions tested, the majority of the strains produced similar banding pattern for any two regions grouped into a cluster. The strains grouped as a genotype were from the same geographical location. Strains collected from each geographical region were also highly heterogeneous. Such analysis is important to identify the genetic clones of the pathogen associated with sporadic infections and disease outbreak to identify the common source and implement public health measures.

Modeling malaria and typhoid fever co-infection dynamics.

PubMed

Mutua, Jones M; Wang, Feng-Bin; Vaidya, Naveen K

2015-06-01

Malaria and typhoid are among the most endemic diseases, and thus, of major public health concerns in tropical developing countries. In addition to true co-infection of malaria and typhoid, false diagnoses due to similar signs and symptoms and false positive results in testing methods, leading to improper controls, are the major challenges on managing these diseases. In this study, we develop novel mathematical models describing the co-infection dynamics of malaria and typhoid. Through mathematical analyses of our models, we identify distinct features of typhoid and malaria infection dynamics as well as relationships associated to their co-infection. The global dynamics of typhoid can be determined by a single threshold (the typhoid basic reproduction number, R0(T)) while two thresholds (the malaria basic reproduction number, R0(M), and the extinction index, R0(MM)) are needed to determine the global dynamics of malaria. We demonstrate that by using efficient simultaneous prevention programs, the co-infection basic reproduction number, R0, can be brought down to below one, thereby eradicating the diseases. Using our model, we present illustrative numerical results with a case study in the Eastern Province of Kenya to quantify the possible false diagnosis resulting from this co-infection. In Kenya, despite having higher prevalence of typhoid, malaria is more problematic in terms of new infections and disease deaths. We find that false diagnosis-with higher possible cases for typhoid than malaria-cause significant devastating impacts on Kenyan societies. Our results demonstrate that both diseases need to be simultaneously managed for successful control of co-epidemics. Copyright © 2015 Elsevier Inc. All rights reserved.

CAUSES OF TYPHOID FEVER IN MASSACHUSETTS

PubMed Central

O'Donnell, George T.

1920-01-01

To decrease its typhoid Massachusetts needs now to prevent contacts, use prophylaxis, and educate its citizens in personal hygiene. Municipal water supplies are practically safe. Flies, food (milk excepted), privies and sewage are together only a small factor in spreading the disease. The human contact factor is the one that must be controlled. PMID:18010326

A rabbit model of non-typhoidal Salmonella bacteremia.

PubMed

Panda, Aruna; Tatarov, Ivan; Masek, Billie Jo; Hardick, Justin; Crusan, Annabelle; Wakefield, Teresa; Carroll, Karen; Yang, Samuel; Hsieh, Yu-Hsiang; Lipsky, Michael M; McLeod, Charles G; Levine, Myron M; Rothman, Richard E; Gaydos, Charlotte A; DeTolla, Louis J

2014-09-01

Bacteremia is an important cause of morbidity and mortality in humans. In this study, we focused on the development of an animal model of bacteremia induced by non-typhoidal Salmonella. New Zealand White rabbits were inoculated with a human isolate of non-typhoidal Salmonella strain CVD J73 via the intra-peritoneal route. Blood samples were collected at specific time points and at euthanasia from infected rabbits. Additionally, tissue samples from the heart, lungs, spleen, gastrointestinal tract, liver and kidneys were obtained at euthanasia. All experimentally infected rabbits displayed clinical signs of disease (fever, dehydration, weight loss and lethargy). Tissues collected at necropsy from the animals exhibited histopathological changes indicative of bacteremia. Non-typhoidal Salmonella bacteria were detected in the blood and tissue samples of infected rabbits by microbiological culture and real-time PCR assays. The development of this animal model of bacteremia could prove to be a useful tool for studying how non-typhoidal Salmonella infections disseminate and spread in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010

PubMed Central

Buckle, Geoffrey C.; Walker, Christa L. Fischer; Black, Robert E.

2012-01-01

Background Typhoid and paratyphoid fever remain important causes of morbidity worldwide. Accurate disease burden estimates are needed to guide policy decisions and prevention and control strategies. Methods We conducted a systematic literature review of the PubMed and Scopus databases using pre-defined criteria to identify population-based studies with typhoid fever incidence data published between 1980 and 2009. We also abstracted data from annual reports of notifiable diseases in countries with advanced surveillance systems. Typhoid and paratyphoid fever input data were grouped into regions and regional incidence and mortality rates were estimated. Incidence data were extrapolated across regions for those lacking data. Age-specific incidence rates were derived for regions where age-specific data were available. Crude and adjusted estimates of the global typhoid fever burden were calculated. Results Twenty-five studies were identified, all of which contained incidence data on typhoid fever and 12 on paratyphoid fever. Five advanced surveillance systems contributed data on typhoid fever; 2 on paratyphoid fever. Regional typhoid fever incidence rates ranged from <0.1/100 000 cases/y in Central and Eastern Europe and Central Asia to 724.6/100 000 cases/y in Sub-Saharan Africa. Regional paratyphoid incidence rates ranged from 0.8/100 000 cases/y in North Africa/Middle East to 77.4/100 000 cases/y in Sub-Saharan Africa and South Asia. The estimated total number of typhoid fever episodes in 2010 was 13.5 million (interquartile range 9.1–17.8 million). The adjusted estimate accounting for the low sensitivity of blood cultures for isolation of the bacteria was 26.9 million (interquartile range 18.3–35.7 million) episodes. These findings are comparable to the most recent analysis of global typhoid fever morbidity, which reported crude and adjusted estimates of 10.8 million and 21.7 million typhoid fever episodes globally in 2000. Conclusion Typhoid fever remains a significant health burden, especially in low- and middle-income countries. Despite the availability of more recent data on both enteric fevers, additional research is needed in many regions, particularly Africa, Latin America and other developing countries. PMID:23198130

"Winged sponges": houseflies as carriers of typhoid fever in 19th- and early 20th-century military camps.

PubMed

Cirillo, Vincent J

2006-01-01

Typhoid fever was the scourge of 19th- and early 20th-century armies. During the Spanish-American War (1898) and the Anglo-Boer War (1899- 1902), typhoid killed more soldiers than enemy bullets. Walter Reed and his coworkers investigated the cause of the typhoid epidemics in the U.S. Army camps and concluded that, next to human contact, the housefly (Musca domestica) was the most active agent in the spread of the disease. British medical officers in South Africa, facing even worse typhoid epidemics, reached the same conclusion. The experiences of the American and British armies finally convinced the medical profession and public health authorities that these insects conveyed typhoid. The housefly was now seen as a health menace. Military and civilian sanitarians waged fly-eradication campaigns that prevented the housefly's access to breeding places (especially human excrement), and that protected food and drink from contamination. Currently, M. domestica is recognized as the mechanical vector of a wide variety of viral, bacterial, and protozoal pathogens. Fly control is still an important public health measure in the 21st century, especially in developing countries.

Salmonella chronic carriage: epidemiology, diagnosis and gallbladder persistence

PubMed Central

Gunn, John S.; Marshall, Joanna M.; Baker, Stephen; Dongol, Sabina; Charles, Richelle C.; Ryan, Edward T.

2014-01-01

Typhoid (enteric fever) remains a major cause of morbidity and mortality worldwide, causing over 21 million new infections annually, with the majority of deaths occurring in young children. As typhoid fever-causing Salmonella have no known environmental reservoir, the chronic, asymptomatic carrier state is thought to be a key feature of continued maintenance of the bacterium within human populations. In spite of the importance of this disease to public health, our understanding of the molecular mechanisms that catalyze carriage, as well as our ability to reliably identify and treat the Salmonella carrier state, have only recently begun to advance. PMID:25065707

Bilateral breast abscess: a rare complication of enteric fever.

PubMed

Singh, S; Pandya, Y; Rathod, J; Trivedi, S

2009-01-01

Breast abscess is usually caused by Staphylococcus aureus in pregnant or lactating females. Salmonella spp. is occasionally associated with abscess formation in various organs, but breast abscess is a very rare complication. In enteric fever dissemination to multiple organ systems following bacteraemia can lead to localized abscess. We report a case of bilateral breast abscess due to Salmonella Typhi in an unmarried 35-year-old female without any predisposing conditions. She presented with fever and painful swelling of both the breasts. S. typhi was isolated from both breasts. Such rare cause must be suspected in females without any evident predisposing factors for effective management.

Revised Ciprofloxacin Breakpoints for Salmonella: Is it Time to Write an Obituary?

PubMed

Girish, Revathy; Kumar, Anil; Khan, Sadia; Dinesh, Kavitha R; Karim, Shamsul

2013-11-01

To determine the minimum inhibitory concentration of ciprofloxacin among 50 blood stream isolates of Salmonella enterica. A total of 50 consecutive isolates of Salmonella enterica were tested for susceptibility to antimicrobials using the Kirby Bauer disk diffusion method. Minimum inhibitory concentrations were determined using Hi-Comb strips. All results were interpreted according to the CLSI guidelines. Of the 50 isolates 70%were Salmonella Typhi, 4% Salmonella paratyphi A, 2% Salmonella paratyphi B and the remaining 10% were identified only as Salmonella species. Using the CLSI 2011 breakpoints for disc diffusion, 86% (43/50) were resistant to nalidixic acid(NA), 22% (11/50) to ciprofloxacin, 12% to azithromycin, 6% to cotrimoxazole, 4% to ampicillin and 1% to chloramphenicol. The MIC50 and MIC90 of ciprofloxacin for S.Typhi were 0.181 μg/mL and 5.06 μg/mL respectively. While the same for S. paratyphi A was 0.212μg/mL and 0.228μg/mL respectively. None of the isolates were multi drug resistant and all were susceptible to ceftriaxone. Using the CLSI 2012 revised ciprofloxacin breakpoints for disc diffusion (>31mm) & MIC (<0.06 μg/mL), 90% (45/50) of these isolates were found to be resistant. MIC's of ciprofloxacin should be reported for all salmonella isolates and should be used to guide treatment. Blindly following western guidelines for a disease which is highly endemic in the subcontinent will spell the death knell of a cheap and effective drug in our armamentarium. Therefore it will be too premature to declare that "the concept of using ciprofloxacin in typhoid fever is dead!"

East London Experience with Enteric Fever 2007-2012

PubMed Central

Dave, Jayshree; Millar, Michael; Maxeiner, Horst; Freedman, Joanne; Meade, Rachel; Rosmarin, Caryn; Jordan, Matthew; Andrews, Nick; Holliman, Richard; Sefton, Armine

2015-01-01

Purpose The clinical presentation and epidemiology for patients with enteric fever at two hospitals in East London during 2007–2012 is described with the aim to identify preventive opportunities and to reduce the cost of treatment. Methods A retrospective analysis of case notes from patients admitted with enteric fever during 2007 to 2012 with a microbiologically confirmed diagnosis was undertaken. Details on clinical presentation, travel history, demographic data, laboratory parameters, treatment, patient outcome and vaccination status were collected. Results Clinical case notes were available for 98/129 (76%) patients including 69 Salmonella enterica serovar Typhi (S. Typhi) and 29 Salmonella enterica serovar Paratyphi (S. Paratyphi). Thirty-four patients (35%) were discharged from emergency medicine without a diagnosis of enteric fever and then readmitted after positive blood cultures. Seventy-one of the 98 patients (72%) were UK residents who had travelled abroad, 23 (23%) were foreign visitors/new entrants to the UK and four (4%) had not travelled abroad. Enteric fever was not considered in the initial differential diagnosis for 48/98 (49%) cases. The median length of hospital stay was 7 days (range 0–57 days). The total cost of bed days for managing enteric fever was £454,000 in the two hospitals (mean £75,666/year). Median time to clinical resolution was five days (range 1–20). Seven of 98 (7%) patients were readmitted with relapsed or continued infection. Six of the 71 (8%) patients had received typhoid vaccination, 34 (48%) patients had not received vaccination, and for 31 cases (44%) vaccination status was unknown. Conclusions Further interventions regarding education and vaccination of travellers and recognition of the condition by emergency medicine clinicians in travellers to South Asia is required. PMID:25790017

Ultra-Fast and Sensitive Detection of Non-Typhoidal Salmonella Using Microwave-Accelerated Metal-Enhanced Fluorescence (“MAMEF”)

PubMed Central

Galen, James E.; Geddes, Chris D.; Levine, Myron M.

2011-01-01

Certain serovars of Salmonella enterica subsp. enterica cause invasive disease (e.g., enteric fever, bacteremia, septicemia, meningitis, etc.) in humans and constitute a global public health problem. A rapid, sensitive diagnostic test is needed to allow prompt initiation of therapy in individual patients and for measuring disease burden at the population level. An innovative and promising new rapid diagnostic technique is microwave-accelerated metal-enhanced fluorescence (MAMEF). We have adapted this assay platform to detect the chromosomal oriC locus common to all Salmonella enterica subsp. enterica serovars. We have shown efficient lysis of biologically relevant concentrations of Salmonella spp. suspended in bacteriological media using microwave-induced lysis. Following lysis and DNA release, as little as 1 CFU of Salmonella in 1 ml of medium can be detected in <30 seconds. Furthermore the assay is sensitive and specific: it can detect oriC from Salmonella serovars Typhi, Paratyphi A, Paratyphi B, Paratyphi C, Typhimurium, Enteritidis and Choleraesuis but does not detect Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae or Acinetobacter baumanii. We have also performed preliminary experiments using a synthetic Salmonella oriC oligonucleotide suspended in whole human blood and observed rapid detection when the sample was diluted 1∶1 with PBS. These pre-clinical data encourage progress to the next step to detect Salmonella in blood (and other ordinarily sterile, clinically relevant body fluids). PMID:21494634

Combination vaccines against diarrheal diseases

PubMed Central

Venkatesan, Malabi M; Van de Verg, Lillian L

2015-01-01

Abstract Diarrheal diseases remain a leading cause of global childhood mortality and morbidity. Several recent epidemiological studies highlight the rate of diarrheal diseases in different parts of the world and draw attention to the impact on childhood growth and survival. Despite the well-documented global burden of diarrheal diseases, currently there are no combination diarrheal vaccines, only licensed vaccines for rotavirus and cholera, and Salmonella typhi-based vaccines for typhoid fever. The recognition of the impact of diarrheal episodes on infant growth, as seen in resource-poor countries, has spurred action from governmental and non-governmental agencies to accelerate research toward affordable and effective vaccines against diarrheal diseases. Both travelers and children in endemic countries will benefit from a combination diarrheal vaccine, but it can be argued that the greater proportion of any positive impact will be on the public health status of the latter. The history of combination pediatric vaccines indicate that monovalent or single disease vaccines are typically licensed first prior to formulation in a combination vaccine, and that the combinations themselves undergo periodic revision in response to need for improvement in safety or potential for wider coverage of important pediatric pathogens. Nevertheless combination pediatric vaccines have proven to be an effective tool in limiting or eradicating communicable childhood diseases worldwide. The landscape of diarrheal vaccine candidates indicates that there now several in active development that offer options for potential testing of combinations to combat those bacterial and viral pathogens responsible for the heaviest disease burden—rotavirus, ETEC, Shigella, Campylobacter, V. cholera and Salmonella. PMID:25891647

Dissemination of Persistent Intestinal Bacteria via the Mesenteric Lymph Nodes Causes Typhoid Relapse▿

PubMed Central

Griffin, Amanda J.; Li, Lin-Xi; Voedisch, Sabrina; Pabst, Oliver; McSorley, Stephen J.

2011-01-01

Enteric pathogens can cause relapsing infections in a proportion of treated patients, but greater understanding of this phenomenon is hindered by the lack of appropriate animal models. We report here a robust animal model of relapsing primary typhoid that initiates after apparently successful antibiotic treatment of susceptible mice. Four days of enrofloxacin treatment were sufficient to reduce bacterial loads below detectable levels in all major organs, and mice appeared otherwise healthy. However, any interruption of further antibiotic therapy allowed renewed fecal shedding and renewed bacterial growth in systemic tissues to occur, and mice eventually succumbed to relapsing infection. In vivo imaging of luminescent Salmonella identified the mesenteric lymph nodes (MLNs) as a major reservoir of relapsing infection. A magnetic-bead enrichment strategy isolated MLN-resident CD11b+ Gr-1− monocytes associated with low numbers of persistent Salmonella. However, the removal of MLNs increased the severity of typhoid relapse, demonstrating that this organ serves as a protective filter to restrain the dissemination of bacteria during antibiotic therapy. Together, these data describe a robust animal model of typhoid relapse and identify an important intestinal phagocyte subset involved in protection against the systemic spread of enteric infection. PMID:21263018

Typhoid fever in children in Africa

PubMed Central

Mweu, Evanson; English, Mike

2008-01-01

Estimates for the year 2000 suggested that there were approximately 21.5 million infections and 200,000 deaths from typhoid fever globally each year, making the disease one of the most serious infectious disease threats to public health on a global scale. However, these estimates were based on little data, especially from Africa. Global prominence and high-profile outbreaks have created the perception in Kenya that typhoid is a common cause of febrile illness. The Widal test is used widely in diagnosis. We have reviewed recent literature, taking the perspective of a healthcare provider, to collate information on the prevalence of typhoid in children particularly, and to explore the role of clinical diagnosis and diagnosis based on a crude, but common, interpretation of the Widal test. Data suggest that typhoid in children in rural Africa is uncommon, perhaps 100 times or 250 times less common than invasive disease because of Haemophilus influenzae or Streptococcus pneumoniae, respectively. Frequent use of the Widal test may result in many hundreds of over-treatment episodes for every true case treated and may perpetuate the perception that typhoid is common. Countries such as Kenya need better bacterial disease surveillance systems allied to better information for healthcare providers to promote appropriate decision-making on prevention and treatment strategies. PMID:18312473

Fever of unknown origin (FUO) in an elderly adult due to Epstein-Barr virus (EBV) presenting as "typhoidal mononucleosis," mimicking a lymphoma.

PubMed

Cunha, Burke A; Petelin, Andrew; George, Sonia

2013-01-01

We describe fever of unknown origin (FUO) in a 57-year-old woman with hepatosplenomegaly. The diagnostic workup was directed at diagnosing a lymphoma. Her history of travel and exposures to food and water did not make typhoid fever a likely diagnostic possibility. Because she presented with prolonged fevers, fatigue, anorexia, weight loss, and night sweats with hepatosplenomegaly, lymphoma was likely. Initially, Epstein-Barr virus (EBV) was not considered because of her age, the absence of pharyngitis and cervical adenopathy, and the higher likelihood of another diagnosis, ie, lymphoma. Eventually, her FUO was diagnosed as EBV presenting as "typhoidal mononucleosis." Typhoidal mononucleosis is an extremely rare presentation of EBV as a cause of FUO in an adult. All of her symptoms as well as her clinical and laboratory findings resolved spontaneously. Copyright © 2013 Elsevier Inc. All rights reserved.

Cytotoxic effector functions of T cells are not required for protective immunity against fatal Rickettsia typhi infection in a murine model of infection: Role of TH1 and TH17 cytokines in protection and pathology

PubMed Central

Rauch, Jessica; Papp, Stefanie; Kuehl, Svenja; Richardt, Ulricke; Fleischer, Bernhard; Osterloh, Anke

2017-01-01

Endemic typhus caused by Rickettsia (R.) typhi is an emerging febrile disease that can be fatal due to multiple organ pathology. Here we analyzed the requirements for protection against R. typhi by T cells in the CB17 SCID model of infection. BALB/c wild-type mice generate CD4+ TH1 and cytotoxic CD8+ T cells both of which are sporadically reactivated in persistent infection. Either adoptively transferred CD8+ or CD4+ T cells protected R. typhi-infected CB17 SCID mice from death and provided long-term control. CD8+ T cells lacking either IFNγ or Perforin were still protective, demonstrating that the cytotoxic function of CD8+ T cells is not essential for protection. Immune wild-type CD4+ T cells produced high amounts of IFNγ, induced the release of nitric oxide in R. typhi-infected macrophages and inhibited bacterial growth in vitro via IFNγ and TNFα. However, adoptive transfer of CD4+IFNγ-/- T cells still protected 30–90% of R. typhi-infected CB17 SCID mice. These cells acquired a TH17 phenotype, producing high amounts of IL-17A and IL-22 in addition to TNFα, and inhibited bacterial growth in vitro. Surprisingly, the neutralization of either TNFα or IL-17A in CD4+IFNγ-/- T cell recipient mice did not alter bacterial elimination by these cells in vivo, led to faster recovery and enhanced survival compared to isotype-treated animals. Thus, collectively these data show that although CD4+ TH1 cells are clearly efficient in protection against R. typhi, CD4+ TH17 cells are similarly protective if the harmful effects of combined production of TNFα and IL-17A can be inhibited. PMID:28222146

Community Acquired Bacteremia in Young Children from Central Nigeria- A Pilot Study

PubMed Central

2011-01-01

Background Reports of the etiology of bacteremia in children from Nigeria are sparse and have been confounded by wide spread non-prescription antibiotic use and suboptimal laboratory culture techniques. We aimed to determine causative agents and underlying predisposing conditions of bacteremia in Nigerian children using data arising during the introduction of an automated blood culture system accessed by 7 hospitals and clinics in the Abuja area. Methods Between September 2008 and November 2009, we enrolled children with clinically suspected bacteremia at rural and urban clinical facilities in Abuja or within the Federal Capital Territory of Nigeria. Blood was cultured using an automated system with antibiotic removing device. We documented clinical features in all children and tested for prior antibiotic use in a random sample of sera from children from each site. Results 969 children aged 2 months-5 years were evaluated. Mean age was 21 ± 15.2 months. All children were not systematically screened but there were 59 (6%) children with established diagnosis of sickle cell disease and 42 (4.3%) with HIV infection. Overall, 212 (20.7%) had a positive blood culture but in only 105 (10.8%) were these considered to be clinically significant. Three agents, Staphylococcus aureus (20.9%), Salmonella typhi (20.9%) and Acinetobacter (12.3%) accounted for over half of the positive cultures. Streptococcus pneumoniae and non-typhi Salmonellae each accounted for 7.6%. Although not the leading cause of bacteremia, Streptococcus pneumoniae was the single leading cause of all deaths that occurred during hospitalization and after hospital discharge. Conclusion S. typhi is a significant cause of vaccine-preventable morbidity while S. pneumoniae may be a leading cause of mortality in this setting. This observation contrasts with reports from most other African countries where non-typhi Salmonellae are predominant in young children. Expanded surveillance is required to confirm the preliminary observations from this pilot study to inform implementation of appropriate public health control measures. PMID:21595963

Plasmid-mediated quinolone resistance in non-Typhi serotypes of Salmonella enterica.

PubMed

Gay, Kathryn; Robicsek, Ari; Strahilevitz, Jacob; Park, Chi Hye; Jacoby, George; Barrett, Timothy J; Medalla, Felicita; Chiller, Tom M; Hooper, David C

2006-08-01

Serious infections with Salmonella species are often treated with fluoroquinolones or extended-spectrum beta-lactams. Increasingly recognized in Enterobacteriaceae, plasmid-mediated quinolone resistance is encoded by qnr genes. Here, we report the presence of qnr variants in human isolates of non-Typhi serotypes of Salmonella enterica (hereafter referred to as non-Typhi Salmonella) from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria. All non-Typhi Salmonella specimens from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria collected from 1996 to 2003 with ciprofloxacin minimum inhibitory concentrations > or = 0.06 microg/mL (233 specimens) and a subset with minimum inhibitory concentrations < or = 0.03 microg/mL (102 specimens) were screened for all known qnr genes (A, B, and S) by polymerase chain reaction. For isolates with positive results, qnr and quinolone resistance-determining region sequences were determined. Plasmids containing qnr genes were characterized by conjugation or transformation. Conjugative plasmids harboring qnrB variants were detected in 7 Salmonella enterica serotype Berta isolates and 1 Salmonella enterica serotype Mbandaka isolate. The S. Mbandaka plasmid also had an extended-spectrum beta -lactamase. Variants of qnrS on nonconjugative plasmids were detected in isolates of Salmonella enterica serotype Anatum and Salmonella enterica serotype Bovismorbificans. Plasmid-mediated quinolone resistance appears to be widely distributed, though it is still uncommon in non-Typhi Salmonella isolates from the United States, including strains that are quinolone susceptible by the criteria of the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). The presence of this gene in non-Typhi Salmonella that causes infection in humans suggests potential for spread through the food supply, which is a public health concern.

Differential Epidemiology of Salmonella Typhi and Paratyphi A in Kathmandu, Nepal: A Matched Case Control Investigation in a Highly Endemic Enteric Fever Setting

PubMed Central

Tran Vu Thieu, Nga; Dongol, Sabina; Le Thi Phuong, Tu; Voong Vinh, Phat; Arjyal, Amit; Martin, Laura B.; Rondini, Simona; Farrar, Jeremy J.; Dolecek, Christiane; Basnyat, Buddha; Baker, Stephen

2013-01-01

Background Enteric fever, a systemic infection caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A, is endemic in Kathmandu, Nepal. Previous work identified proximity to poor quality water sources as a community-level risk for infection. Here, we sought to examine individual-level risk factors related to hygiene and sanitation to improve our understanding of the epidemiology of enteric fever in this setting. Methodology and principal findings A matched case-control analysis was performed through enrollment of 103 blood culture positive enteric fever patients and 294 afebrile community-based age and gender-matched controls. A detailed questionnaire was administered to both cases and controls and the association between enteric fever infection and potential exposures were examined through conditional logistic regression. Several behavioral practices were identified as protective against infection with enteric fever, including water storage and hygienic habits. Additionally, we found that exposures related to poor water and socioeconomic status are more influential in the risk of infection with S. Typhi, whereas food consumption habits and migration play more of a role in risk of S. Paratyphi A infection. Conclusions and significance Our work suggests that S. Typhi and S. Paratyphi A follow different routes of infection in this highly endemic setting and that sustained exposure to both serovars probably leads to the development of passive immunity. In the absence of a polyvalent vaccine against S. Typhi and S. Paratyphi A, we advocate better systems for water treatment and storage, improvements in the quality of street food, and vaccination with currently available S. Typhi vaccines. PMID:23991240

The burden and characteristics of enteric fever at a healthcare facility in a densely populated area of Kathmandu.

PubMed

Karkey, Abhilasha; Arjyal, Amit; Anders, Katherine L; Boni, Maciej F; Dongol, Sabina; Koirala, Samir; My, Phan Vu Tra; Nga, Tran Vu Thieu; Clements, Archie C A; Holt, Kathryn E; Duy, Pham Thanh; Day, Jeremy N; Campbell, James I; Dougan, Gordon; Dolecek, Christiane; Farrar, Jeremy; Basnyat, Buddha; Baker, Stephen

2010-11-15

Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A) remains a major public health problem in many settings. The disease is limited to locations with poor sanitation which facilitates the transmission of the infecting organisms. Efficacious and inexpensive vaccines are available for S. Typhi, yet are not commonly deployed to control the disease. Lack of vaccination is due partly to uncertainty of the disease burden arising from a paucity of epidemiological information in key locations. We have collected and analyzed data from 3,898 cases of blood culture-confirmed enteric fever from Patan Hospital in Lalitpur Sub-Metropolitan City (LSMC), between June 2005 and May 2009. Demographic data was available for a subset of these patients (n = 527) that were resident in LSMC and who were enrolled in trials. We show a considerable burden of enteric fever caused by S. Typhi (2,672; 68.5%) and S. Paratyphi A (1,226; 31.5%) at this Hospital over a four year period, which correlate with seasonal fluctuations in rainfall. We found that local population density was not related to incidence and we identified a focus of infections in the east of LSMC. With data from patients resident in LSMC we found that the median age of those with S. Typhi (16 years) was significantly less than S. Paratyphi A (20 years) and that males aged 15 to 25 were disproportionately infected. Our findings provide a snapshot into the epidemiological patterns of enteric fever in Kathmandu. The uneven distribution of enteric fever patients within the population suggests local variation in risk factors, such as contaminated drinking water. These findings are important for initiating a vaccination scheme and improvements in sanitation. We suggest any such intervention should be implemented throughout the LSMC area.

A Case Control Study of Incident Rheumatological Conditions Following Acute Gastroenteritis During Military Deployment

DTIC Science & Technology

2013-01-01

commonly caused by diarrhoeagenic Escherichia coli, Campylobacter spp., Shigella spp. and non- typhoidal Salmonella spp., although viral and parasitic...and coli, non-typhoidal Salmonella spp, Shigella spp and Yersinia enterocolitica.9–13 Reports of ReA following bacterial gastroenteritis are most...significantly with age. In a prospective study of culture-confirmed Campylobacter, E coli O157, Salmonella, Shigella and Yersinia infections among

Vaccines against invasive Salmonella disease

PubMed Central

MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

2014-01-01

Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

A Multicountry Molecular Analysis of Salmonella enterica Serovar Typhi With Reduced Susceptibility to Ciprofloxacin in Sub-Saharan Africa

PubMed Central

Al-Emran, Hassan M.; Eibach, Daniel; Krumkamp, Ralf; Ali, Mohammad; Baker, Stephen; Biggs, Holly M.; Bjerregaard-Andersen, Morten; Breiman, Robert F.; Clemens, John D.; Crump, John A.; Cruz Espinoza, Ligia Maria; Deerin, Jessica; Dekker, Denise Myriam; Gassama Sow, Amy; Hertz, Julian T.; Im, Justin; Ibrango, Samuel; von Kalckreuth, Vera; Kabore, Leon Parfait; Konings, Frank; Løfberg, Sandra Valborg; Meyer, Christian G.; Mintz, Eric D.; Montgomery, Joel M.; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Razafindrabe, Jean Luco Tsiriniaina; Rabezanahary, Henintsoa; Rakotondrainiarivelo, Jean Philibert; Rakotozandrindrainy, Raphaël; Raminosoa, Tiana Mirana; Schütt-Gerowitt, Heidi; Sampo, Emmanuel; Soura, Abdramane Bassiahi; Tall, Adama; Warren, Michelle; Wierzba, Thomas F.; May, Jürgen; Marks, Florian

2016-01-01

Background. Salmonella enterica serovar Typhi is a predominant cause of bloodstream infections in sub-Saharan Africa (SSA). Increasing numbers of S. Typhi with resistance to ciprofloxacin have been reported from different parts of the world. However, data from SSA are limited. In this study, we aimed to measure the ciprofloxacin susceptibility of S. Typhi isolated from patients with febrile illness in SSA. Methods. Febrile patients from 9 sites within 6 countries in SSA with a body temperature of ≥38.0°C were enrolled in this study. Blood samples were obtained for bacterial culture, and Salmonella isolates were identified biochemically and confirmed by multiplex polymerase chain reaction (PCR). Antimicrobial susceptibility of all Salmonella isolates was performed by disk diffusion test, and minimum inhibitory concentrations (MICs) against ciprofloxacin were measured by Etest. All Salmonella isolates with reduced susceptibility to ciprofloxacin (MIC > 0.06 µg/mL) were screened for mutations in quinolone resistance-determining regions in target genes, and the presence of plasmid-mediated quinolone resistance (PMQR) genes was assessed by PCR. Results. A total of 8161 blood cultures were performed, and 100 (1.2%) S. Typhi, 2 (<0.1%) Salmonella enterica serovar Paratyphi A, and 27 (0.3%) nontyphoid Salmonella (NTS) were isolated. Multidrug-resistant S. Typhi were isolated in Kenya (79% [n = 38]) and Tanzania (89% [n = 8]) only. Reduced ciprofloxacin-susceptible (22% [n = 11]) S. Typhi were isolated only in Kenya. Among those 11 isolates, all had a Glu133Gly mutation in the gyrA gene combined with either a gyrA (Ser83Phe) or gyrB mutation (Ser464Phe). One Salmonella Paratyphi A isolate with reduced susceptibility to ciprofloxacin was found in Senegal, with 1 mutation in gyrA (Ser83Phe) and a second mutation in parC (Ser57Phe). Mutations in the parE gene and PMQR genes were not detected in any isolate. Conclusions. Salmonella Typhi with reduced susceptibility to ciprofloxacin was not distributed homogenously throughout SSA. Its prevalence was very high in Kenya, and was not observed in other study countries. Continuous monitoring of antimicrobial susceptibility is required to follow the potential spread of antimicrobial-resistant isolates throughout SSA. PMID:26933020

Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study.

PubMed

Mohan, Vadrevu Krishna; Varanasi, Vineeth; Singh, Anit; Pasetti, Marcela F; Levine, Myron M; Venkatesan, Ramasamy; Ella, Krishna M

2015-08-01

Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age. Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6-23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots. After 2 years, subsets in each group received a booster dose. The primary objective included analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline (seroconversion [SCN]) 42 days after immunization. Typbar-TCV recipients in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%; GMT, 1293 [95% confidence interval {CI}, 1153-1449]) than recipients of Typbar (SCN, 93%; GMT, 411 [95% CI, 359-471]) (P < .001). Typbar-TCV was highly immunogenic in the OLT (SCN, 98%; GMT, 1937 [95% CI, 1785-2103]). Two years after vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 [95% CI, 73-92]); and exhibited higher avidity (geometric mean avidity index [GMAI], 60%) than in Typbar recipients (GMT, 46 [95% CI, 40-53]; GMAI 46%) in the RCT (P < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42-55) and GMAI of 57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in all ages. No serious vaccine-attributable adverse events were observed. Single-dose Typbar-TCV is well tolerated and induces robust and long-lasting serum anti-Vi IgG across age groups. CTRI/2011/08/001957, CTRI/2014/01/004341. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Typhoid Vaccine Acceleration Consortium (TyVAC): Vaccine effectiveness study designs: Accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. Report from a meeting held on 26-27 October 2016, Oxford, UK.

PubMed

Meiring, James E; Gibani, Malick

2017-09-12

Typhoid fever is estimated to cause between 11.9-26.9 million infections globally each year with 129,000-216,510 deaths. Access to improved water sources have reduced disease incidence in parts of the world but the use of efficacious vaccines is seen as an important public health tool for countries with a high disease burden. A new generation of Vi typhoid conjugate vaccines (TCVs), licensed for use in young children and expected to provide longer lasting protection than previous vaccines, are now available. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has convened a working group to review the evidence on TCVs and produce an updated WHO position paper for all typhoid vaccines in 2018 that will inform Gavi, the Vaccine Alliance's future vaccine investment strategies for TCVs. The Typhoid Vaccine Acceleration Consortium (TyVAC) has been formed through a $36.9 million funding program from the Bill & Melinda Gates Foundation to accelerate the introduction of TCVs into Gavi-eligible countries. In October 2016, a meeting was held to initiate planning of TCV effectiveness studies that will provide the data required by policy makers and stakeholders to support decisions on TCV use in countries with a high typhoid burden. Discussion topics included (1) the latest evidence and data gaps in typhoid epidemiology; (2) WHO and Gavi methods and data requirements; (3) data on TCV efficacy; (4) cost effectiveness analysis for TCVs from mathematical models; (5) TCV delivery and effectiveness study design. Specifically, participants were asked to comment on study design in 3 sites for which population-based typhoid surveillance is underway. The conclusion of the meeting was that country-level decision making would best be informed by the respective selected sites in Africa and Asia vaccinating children aged from 9-months to 15-years-old, employing either an individual or cluster randomized design with design influenced by population characteristics, transmission dynamics, and statistical considerations. Copyright © 2017.

[Wilms' tumor, multiple intestinal parasitosis and typhoid fever].

PubMed

Franco Vega, G; Llausás Vargas, A; Kumate, J

1977-01-01

The case was that of a 21-month-old infant who presented a great inoperable Wilm's tumor that was treated with vincristine to the point of practically disappearing. Severe typhoid fever that was complicated by multiple intestinal parasitoses (ascariasis, trichuriasis, giardiasis and strongyloidiasis) appeared. Possibly, tumoral necrosis, salmonellosis and the parasitoses formed a sac that opened to the hepatic angle of the colon. Finally, multiple liver metastases were discovered and confirmed pathologically. The patient died 36 hours after surgical reexamination and liver biopsies, from causes not clearly explained. Comments are made on the diagnostic problems originated by rareness of the association of typhoid fever resistant to chloramphenicol, intestinal parasitoses and a great Wilms' tumor and the possible influence of chemotherapy and radiotherapy in the evolution of the case.

Louis I. Dublin and the development of the observational study: the Metropolitan Life Insurance Company natural history (cohort) studies of typhoid fever and scarlet fever.

PubMed

Lilienfeld, David E

2009-06-01

During 1911-1914, using the resources of the Metropolitan Life Insurance Company, Louis I. Dublin conducted two national studies into the survival of those surviving episodes of typhoid fever or scarlet fever. He identified an elevated risk of such mortality, associated with specific causes of death, among those having had typhoid fever but not among the scarlet fever survivors. The studies were methodologically sophisticated, resembling those conducted three to four decades later. The studies appear to have been accepted by the medical and public health communities. However, the absence of modern data processing technology and the lack of financial support for such studies by other investigators precluded the further development of modern epidemiology until World War II.

Invasive Non-typhoidal Salmonella Disease – epidemiology, pathogenesis and diagnosis

PubMed Central

Gordon, Melita A

2012-01-01

Purpose of review To highlight and discuss important publications over the past 12 months providing new insights on invasive non-typhoidal Salmonella disease (iNTS). Recent findings There have been informative new estimates of the burden of iNTS in Asia and in high-resource low-incidence settings. Important information has emerged in the last year about the relationships between HIV, malaria, iNTS and typhoid fever in adults and children in Africa. HIV causes susceptibility to iNTS disease, but has been shown to be protective against typhoid fever. Clinical guidelines for presumptive diagnosis frequently fail to identify iNTS disease in Africa, and there remains a need for improved diagnostic tools. Experimental studies in humans have helped us to understand the intracellular pathogenesis of iNTS and to direct the search for appropriate protein vaccine targets. Summary The most important remaining gap in our knowledge is probably an understanding of how NTS are transmitted, and the nature of the relationship between diarrhoeal disease, carriage and invasive disease in Africa, so that diagnostic and prevention tools can be appropriately directed. PMID:21844803

Development of an Acid-Resistant Salmonella Typhi Ty21a Attenuated Vector For Improved Oral Vaccine Delivery.

PubMed

Dharmasena, Madushini N; Feuille, Catherine M; Starke, Carly Elizabeth C; Bhagwat, Arvind A; Stibitz, Scott; Kopecko, Dennis J

The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella enterica serovar Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, Ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with Ty21a in an enteric-coated capsule (ECC). Several studies have shown that efficacy is reduced when Ty21a is administered in an ECC versus as a buffered liquid formulation, the former limiting exposure to GI tract lymphoid tissues. However, the ECC was selected as a more practical delivery format for both packaging/shipping and vaccine administration ease. We have sought to increase Ty21a acid-resistance to allow for removal from the ECC and immune enhancement. To improve Ty21a acid-resistance, glutamate-dependent acid resistance genes (GAD; responsible for Shigella spp. survival at very low pH) were cloned on a multi-copy plasmid (pGad) under a controllable arabinose-inducible promoter. pGad enhanced acid survival of Ty21a by 5 logs after 3 hours at pH 2.5, when cells were pre-grown in arabinose and under conditions that promote an acid-tolerance response (ATR). For genetically 100% stable expression, we inserted the gad genes into the Ty21a chromosome, using a method that allowed for subsequent removal of a selectable antibiotic resistance marker. Further, both bacterial growth curves and survival assays in cultured human monocytes/macrophages suggest that neither the genetic methods employed nor the resulting acid-resistance conferred by expression of the Gad proteins in Ty21a had any effect on the existing attenuation of this vaccine strain.

Typhoid Fever and Its Association with Environmental Factors in the Dhaka Metropolitan Area of Bangladesh: A Spatial and Time-Series Approach

PubMed Central

Dewan, Ashraf M.; Corner, Robert; Hashizume, Masahiro; Ongee, Emmanuel T.

2013-01-01

Typhoid fever is a major cause of death worldwide with a major part of the disease burden in developing regions such as the Indian sub-continent. Bangladesh is part of this highly endemic region, yet little is known about the spatial and temporal distribution of the disease at a regional scale. This research used a Geographic Information System to explore, spatially and temporally, the prevalence of typhoid in Dhaka Metropolitan Area (DMA) of Bangladesh over the period 2005–9. This paper provides the first study of the spatio-temporal epidemiology of typhoid for this region. The aims of the study were: (i) to analyse the epidemiology of cases from 2005 to 2009; (ii) to identify spatial patterns of infection based on two spatial hypotheses; and (iii) to determine the hydro-climatological factors associated with typhoid prevalence. Case occurrences data were collected from 11 major hospitals in DMA, geocoded to census tract level, and used in a spatio-temporal analysis with a range of demographic, environmental and meteorological variables. Analyses revealed distinct seasonality as well as age and gender differences, with males and very young children being disproportionately infected. The male-female ratio of typhoid cases was found to be 1.36, and the median age of the cases was 14 years. Typhoid incidence was higher in male population than female (χ2 = 5.88, p<0.05). The age-specific incidence rate was highest for the 0–4 years age group (277 cases), followed by the 60+ years age group (51 cases), then there were 45 cases for 15–17 years, 37 cases for 18–34 years, 34 cases for 35–39 years and 11 cases for 10–14 years per 100,000 people. Monsoon months had the highest disease occurrences (44.62%) followed by the pre-monsoon (30.54%) and post-monsoon (24.85%) season. The Student's t test revealed that there is no significant difference on the occurrence of typhoid between urban and rural environments (p>0.05). A statistically significant inverse association was found between typhoid incidence and distance to major waterbodies. Spatial pattern analysis showed that there was a significant clustering of typhoid distribution in the study area. Moran's I was highest (0.879; p<0.01) in 2008 and lowest (0.075; p<0.05) in 2009. Incidence rates were found to form three large, multi-centred, spatial clusters with no significant difference between urban and rural rates. Temporally, typhoid incidence was seen to increase with temperature, rainfall and river level at time lags ranging from three to five weeks. For example, for a 0.1 metre rise in river levels, the number of typhoid cases increased by 4.6% (95% CI: 2.4–2.8) above the threshold of 4.0 metres (95% CI: 2.4–4.3). On the other hand, with a 1°C rise in temperature, the number of typhoid cases could increase by 14.2% (95% CI: 4.4–25.0). PMID:23359825

Genotyping of Salmonella enterica serovar Typhi strains isolated from 1959 to 2006 in China and analysis of genetic diversity by genomic microarray.

PubMed

Zhang, Haifang; Zhang, Xiaolei; Yan, Meiying; Pang, Bo; Kan, Biao; Xu, Huaxi; Huang, Xinxiang

2011-12-15

To determine the genotype of Salmonella enterica serovar Typhi (S. Typhi) strains in China and analyze their genetic diversity. We collected S. Typhi strains from 1959 to 2006 in five highly endemic Chinese provinces and chose 40 representative strains. Multilocus sequence typing was used to determine the genotypes or sequence types (ST) and microarray-based comparative genomic hybridization (M-CGH) to investigate the differences in gene content among these strains. Forty representative S. Typhi strains belonged to 4 sequence types (ST1, ST2, ST890, and ST892). The predominant S. Typhi genotype (31/40) was ST2 and it had a diverse geographic distribution. We discovered two novel STs - ST890 and ST892. M-CGH showed that 69 genes in these two novel STs were divergent from S. Typhi Ty2, which belongs to ST1. In addition, 5 representative Typhi strains of ST2 isolated from Guizhou province showed differences in divergent genes. We determined two novel sequence types, ST890 and ST892, and found that ST2 was the most prevalent genotype of S. Typhi in China. Genetic diversity was present even within a highly clonal bacterial population.

Laboratory-acquired infections of Salmonella enterica serotype Typhi in South Africa: phenotypic and genotypic analysis of isolates.

PubMed

Smith, Anthony Marius; Smouse, Shannon Lucrecia; Tau, Nomsa Pauline; Bamford, Colleen; Moodley, Vineshree Mischka; Jacobs, Charlene; McCarthy, Kerrigan Mary; Lourens, Adré; Keddy, Karen Helena

2017-09-29

Workers in clinical microbiology laboratories are exposed to a variety of pathogenic microorganisms. Salmonella species is among the most commonly reported bacterial causes of laboratory-acquired infections. We report on three cases of laboratory-acquired Salmonella enterica serotype Typhi (Salmonella Typhi) infection which occurred over the period 2012 to 2016 in South Africa. Laboratory investigation included phenotypic and genotypic characterization of isolates. Phenotypic analysis included standard microbiological identification techniques, serotyping and antimicrobial susceptibility testing. Genotypic analysis included the molecular subtyping methodologies of pulsed-field gel electrophoresis analysis, multilocus sequence typing and whole-genome sequencing (WGS); with WGS data analysis including phylogenetic analysis based upon comparison of single nucleotide polymorphism profiles of isolates. All cases of laboratory-acquired infection were most likely the result of lapses in good laboratory practice and laboratory safety. The following critical issues were highlighted. There was misdiagnosis and misreporting of Salmonella Typhi as nontyphoidal Salmonella by a diagnostic laboratory, with associated public health implications. We highlight issues concerning the importance of accurate fluoroquinolone susceptibility testing and interpretation of results according to updated guidelines. We describe potential shortcomings of a single disk susceptibility screening test for fluoroquinolone susceptibility and suggest that confirmatory minimum inhibitory concentration testing should always be performed in cases of invasive Salmonella infections. These antimicrobial susceptibility testing issues resulted in inappropriate ciprofloxacin therapy which may have been responsible for failure in clearance of pathogen from patients. Salmonella Typhi capsular polysaccharide vaccine was not protective in one case, possibly secondarily to a faulty vaccine. Molecular subtyping of isolates proved effective to investigate the genetic relatedness of isolates. Molecular subtyping data interpreted together with epidemiological data allowed us to pinpoint the most likely sources for our cases of laboratory-acquired infection.

An Inducible and Secreted Eukaryote-Like Serine/Threonine Kinase of Salmonella enterica Serovar Typhi Promotes Intracellular Survival and Pathogenesis

PubMed Central

Theeya, Nagaraja; Ta, Atri; Das, Sayan; Mandal, Rahul S.; Chakrabarti, Oishee; Chakrabarti, Saikat; Ghosh, Amar N.

2014-01-01

Eukaryote-like serine/threonine kinases (eSTKs) constitute an important family of bacterial virulence factors. Genome analysis had predicted putative eSTKs in Salmonella enterica serovar Typhi, although their functional characterization and the elucidation of their role in pathogenesis are still awaited. We show here that the primary sequence and secondary structure of the t4519 locus of Salmonella Typhi Ty2 have all the signatures of eukaryotic superfamily kinases. t4519 encodes a ∼39-kDa protein (T4519), which shows serine/threonine kinase activities in vitro. Recombinant T4519 (rT4519) is autophosphorylated and phosphorylates the universal substrate myelin basic protein. Infection of macrophages results in decreased viability of the mutant (Ty2Δt4519) strain, which is reversed by gene complementation. Moreover, reactive oxygen species produced by the macrophages signal to the bacteria to induce T4519, which is translocated to the host cell cytoplasm. That T4519 may target a host substrate(s) is further supported by the activation of host cellular signaling pathways and the induction of cytokines/chemokines. Finally, the role of T4519 in the pathogenesis of Salmonella Typhi is underscored by the significantly decreased mortality of mice infected with the Ty2Δt4519 strain and the fact that the competitive index of this strain for causing systemic infection is 0.25% that of the wild-type strain. This study characterizes the first eSTK of Salmonella Typhi and demonstrates its role in promoting phagosomal survival of the bacteria within macrophages, which is a key determinant of pathogenesis. This, to the best of our knowledge, is the first study to describe the essential role of eSTKs in the in vivo pathogenesis of Salmonella spp. PMID:25404028

Modelling typhoid risk in Dhaka Metropolitan Area of Bangladesh: the role of socio-economic and environmental factors

PubMed Central

2013-01-01

Background Developing countries in South Asia, such as Bangladesh, bear a disproportionate burden of diarrhoeal diseases such as Cholera, Typhoid and Paratyphoid. These seem to be aggravated by a number of social and environmental factors such as lack of access to safe drinking water, overcrowdedness and poor hygiene brought about by poverty. Some socioeconomic data can be obtained from census data whilst others are more difficult to elucidate. This study considers a range of both census data and spatial data from other sources, including remote sensing, as potential predictors of typhoid risk. Typhoid data are aggregated from hospital admission records for the period from 2005 to 2009. The spatial and statistical structures of the data are analysed and Principal Axis Factoring is used to reduce the degree of co-linearity in the data. The resulting factors are combined into a Quality of Life index, which in turn is used in a regression model of typhoid occurrence and risk. Results The three Principal Factors used together explain 87% of the variance in the initial candidate predictors, which eminently qualifies them for use as a set of uncorrelated explanatory variables in a linear regression model. Initial regression result using Ordinary Least Squares (OLS) were disappointing, this was explainable by analysis of the spatial autocorrelation inherent in the Principal factors. The use of Geographically Weighted Regression caused a considerable increase in the predictive power of regressions based on these factors. The best prediction, determined by analysis of the Akaike Information Criterion (AIC) was found when the three factors were combined into a quality of life index, using a method previously published by others, and had a coefficient of determination of 73%. Conclusions The typhoid occurrence/risk prediction equation was used to develop the first risk map showing areas of Dhaka Metropolitan Area whose inhabitants are at greater or lesser risk of typhoid infection. This, coupled with seasonal information on typhoid incidence also reported in this paper, has the potential to advise public health professionals on developing prevention strategies such as targeted vaccination. PMID:23497202

Modelling typhoid risk in Dhaka metropolitan area of Bangladesh: the role of socio-economic and environmental factors.

PubMed

Corner, Robert J; Dewan, Ashraf M; Hashizume, Masahiro

2013-03-16

Developing countries in South Asia, such as Bangladesh, bear a disproportionate burden of diarrhoeal diseases such as cholera, typhoid and paratyphoid. These seem to be aggravated by a number of social and environmental factors such as lack of access to safe drinking water, overcrowdedness and poor hygiene brought about by poverty. Some socioeconomic data can be obtained from census data whilst others are more difficult to elucidate. This study considers a range of both census data and spatial data from other sources, including remote sensing, as potential predictors of typhoid risk. Typhoid data are aggregated from hospital admission records for the period from 2005 to 2009. The spatial and statistical structures of the data are analysed and principal axis factoring is used to reduce the degree of co-linearity in the data. The resulting factors are combined into a quality of life index, which in turn is used in a regression model of typhoid occurrence and risk. The three principal factors used together explain 87% of the variance in the initial candidate predictors, which eminently qualifies them for use as a set of uncorrelated explanatory variables in a linear regression model. Initial regression result using ordinary least squares (OLS) were disappointing, this was explainable by analysis of the spatial autocorrelation inherent in the principal factors. The use of geographically weighted regression caused a considerable increase in the predictive power of regressions based on these factors. The best prediction, determined by analysis of the Akaike information criterion (AIC) was found when the three factors were combined into a quality of life index, using a method previously published by others, and had a coefficient of determination of 73%. The typhoid occurrence/risk prediction equation was used to develop the first risk map showing areas of Dhaka metropolitan area whose inhabitants are at greater or lesser risk of typhoid infection. This, coupled with seasonal information on typhoid incidence also reported in this paper, has the potential to advise public health professionals on developing prevention strategies such as targeted vaccination.

[About problems of carriers of Salmonella typhi and paratyphi B under hygienic, epidemiologic and sociologic view (authors transl)].

PubMed

Brossmann, D

1977-01-01

The carriers of salmonella typhi and paratyphi B are the central figures of the epidemiology of typhoid illnesses. The files available at the medical authorities' office of the Hansestadt Lübeck, with regards to all 543 carriers registered up to 1972, have been analysed, and 102 of 108 carriers who were inhabitants of Lübeck on 31.10.72, have been interviewed in their lodgings.--Following results are mentionable: 1. 55 carriers have been traced during a hospital stay, 22 of them were under hospital treatment because of cholecystectomy. 2. The circle of persons to be obligated for medical examination as per $ 17 of the Federal Republic of Germany's law of epidemics has proved as too small. For instance two female carriers--known since years--did their job without any hindering as plates washer or waitress in restaurants. 3. 21 persons=4% of the patients excreted salmonellae in urine only. 4. 10% of the carriers of salmonella typhi and 16% of the carriers of salmonella paratypi B had in their faeces as least 5-years intervals of non-excretion. 5. The precentage of carriers with at least 5-years intervals of non-excretion in urine was significantly larger than the corresponding percentage in faeces. 6. Falling ill of 280 persons out of the environs of the carriers have been lead back to the latters. 73% of these infections were placed by the carriers before their detection through the medical authorities' office. 7. For 10 patients whose health was recreated excretion did not cease promptly after the cholecystecystectomy. Salmonellae had been found in the faeces for several months more, at two persons even two years after the operation. 8. For 8 carriers a final decision with regards to the success of cholecystectomy is impossible because they denied a duodenal soundation. 9. 123 persons of 23% of total 543 carriers had--before their ascertation--professions not allowed for those persons. Efforts for a successful job arrangement, possibly combined with a change in profession, always met to obstacles. 10. More than 80% of the carriers who were interviewed ignored the directions about personal hygiene. 11. Difficulties arose during a stay in sanatories, hospitals and old age homes. 12. While 60 of the carriers contemplate their situation with indifference other 42 patients are psychically influenced. 5 of them suffer from a psychical trauma. 13. The environment often tends to overrate the danger resulting from carriers. 14. Information of the carriers must be improved.

Assessment of water, sanitation and hygiene interventions in response to an outbreak of typhoid fever in Neno District, Malawi.

PubMed

Bennett, Sarah D; Lowther, Sara A; Chingoli, Felix; Chilima, Benson; Kabuluzi, Storn; Ayers, Tracy L; Warne, Thomas A; Mintz, Eric

2018-01-01

On May 2, 2009 an outbreak of typhoid fever began in rural villages along the Malawi-Mozambique border resulting in 748 illnesses and 44 deaths by September 2010. Despite numerous interventions, including distribution of WaterGuard (WG) for in-home water treatment and education on its use, cases of typhoid fever continued. To inform response activities during the ongoing Typhoid outbreak information on knowledge, attitudes, and practices surrounding typhoid fever, safe water, and hygiene were necessary to plan future outbreak interventions. In September 2010, a survey was administered to female heads in randomly selected households in 17 villages in Neno District, Malawi. Stored household drinking water was tested for free chlorine residual (FCR) levels using the N,N diethyl-p-phenylene diamine colorimetric method (HACH Company, Loveland, CO, USA). Attendance at community-wide educational meetings was reported by 56% of household respondents. Respondents reported that typhoid fever is caused by poor hygiene (77%), drinking unsafe water (49%), and consuming unsafe food (25%), and that treating drinking water can prevent it (68%). WaterGuard, a chlorination solution for drinking water treatment, was observed in 112 (56%) households, among which 34% reported treating drinking water. FCR levels were adequate (FCR ≥ 0.2 mg/L) in 29 (76%) of the 38 households who reported treatment of stored water and had stored water available for testing and an observed bottle of WaterGuard in the home. Soap was observed in 154 (77%) households, among which 51% reported using soap for hand washing. Educational interventions did not reach almost one-half of target households and knowledge remains low. Despite distribution and promotion of WaterGuard and soap during the outbreak response, usage was low. Future interventions should focus on improving water, sanitation and hygiene knowledge, practices, and infrastructure. Typhoid vaccination should be considered.

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS.

PubMed

Nichols, J L

1899-03-01

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm.

Assessment of water, sanitation and hygiene interventions in response to an outbreak of typhoid fever in Neno District, Malawi

PubMed Central

Lowther, Sara A.; Chingoli, Felix; Chilima, Benson; Kabuluzi, Storn; Ayers, Tracy L.; Warne, Thomas A.; Mintz, Eric

2018-01-01

On May 2, 2009 an outbreak of typhoid fever began in rural villages along the Malawi-Mozambique border resulting in 748 illnesses and 44 deaths by September 2010. Despite numerous interventions, including distribution of WaterGuard (WG) for in-home water treatment and education on its use, cases of typhoid fever continued. To inform response activities during the ongoing Typhoid outbreak information on knowledge, attitudes, and practices surrounding typhoid fever, safe water, and hygiene were necessary to plan future outbreak interventions. In September 2010, a survey was administered to female heads in randomly selected households in 17 villages in Neno District, Malawi. Stored household drinking water was tested for free chlorine residual (FCR) levels using the N,N diethyl-p-phenylene diamine colorimetric method (HACH Company, Loveland, CO, USA). Attendance at community-wide educational meetings was reported by 56% of household respondents. Respondents reported that typhoid fever is caused by poor hygiene (77%), drinking unsafe water (49%), and consuming unsafe food (25%), and that treating drinking water can prevent it (68%). WaterGuard, a chlorination solution for drinking water treatment, was observed in 112 (56%) households, among which 34% reported treating drinking water. FCR levels were adequate (FCR ≥ 0.2 mg/L) in 29 (76%) of the 38 households who reported treatment of stored water and had stored water available for testing and an observed bottle of WaterGuard in the home. Soap was observed in 154 (77%) households, among which 51% reported using soap for hand washing. Educational interventions did not reach almost one-half of target households and knowledge remains low. Despite distribution and promotion of WaterGuard and soap during the outbreak response, usage was low. Future interventions should focus on improving water, sanitation and hygiene knowledge, practices, and infrastructure. Typhoid vaccination should be considered. PMID:29474394

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS

PubMed Central

Nichols, Joseph Longworth

1899-01-01

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm. PMID:19866906

Direct evidence of Rickettsia typhi infection in Rhipicephalus sanguineus ticks and their canine hosts.

PubMed

Dzul-Rosado, Karla; Lugo-Caballero, Cesar; Tello-Martin, Raul; López-Avila, Karina; Zavala-Castro, Jorge

2017-01-01

Murine typhus is a rickettsiosis caused by Rickettsia typhi , whose transmission is carried out by rat fleas in urban settlements as classically known, but it also has been related to cat fleas in a sub-urban alternative cycle that has been suggested by recent reports. These studies remarks that in addition to rats, other animals like cats, opossums and dogs could be implied in the transmission of Rickettsia typhi as infected fleas obtained from serologically positive animals have been detected in samples from endemic areas. In Mexico, the higher number of murine typhus cases have been detected in the Yucatan peninsula, which includes a great southeastern region of Mexico that shows ecologic characteristics similar to the sub-urban alternative cycle recently described in Texas and California at the United States. To find out which are the particular ecologic characteristics of murine typhus transmission in this region, we analyzed blood and Rhipicephalus sanguineus ticks obtained from domestic dogs by molecular approaches, demonstrating that both samples were infected by Rickettsia typhi . Following this, we obtained isolates that were analyzed by genetic sequencing to corroborate this infection in 100% of the analyzed samples. This evidence suggests for the first time that ticks and dogs could be actively participating in the transmission of murine typhus, in a role that requires further studies for its precise description.

BERNA: a century of immunobiological innovation.

PubMed

Cryz, S J

1999-10-01

At the time the Swiss Serum and Vaccine Institute Berne (BERNA) was found in 1898, few vaccines or immune globulins were available. This short list included vaccines against cholera, typhoid fever, plague, smallpox and rabies and equine anti-tetanus and diphtheria immune globulins. Furthermore, their use was restricted due to limited production capacity, uncertainty regarding safety and no public health infrastructure to promote their utilization. Today, safe and effective vaccines exist for more than 30 infectious diseases while human hyperimmune globulins exist to treat or prevent rabies, tetanus, respiratory syncytial virus, cytomegalovirus, hepatitis A, hepatitis B, and herpes virus (Varicella zoster) infections. Throughout its 100 years of existence, BERNA has played a key role in the evolution of the field by introducing novel technology leading to safer, and more efficacious vaccines. It was a pioneer in the development of freeze dried smallpox vaccine free from bacterial contamination. The Salmonella typhi Ty21a typhoid fever vaccine strain demonstrated that oral immunization against enteric bacterial pathogens was not only feasible, but could be accomplished with a virtual lack of attendant adverse reactions. This finding has served as an impetus to develop other live attenuated bacterial strains not only as vaccines, but also as vectors for vaccine antigens and gene therapy. One such example is Vibrio cholerae CVD 103-HgR, the first live vaccine for human use derived through recombinant DNA technology. Subsequent studies have shown that these two vaccine strains can be combined without sacrificing safety or immunogenicity, setting the cornerstone for combined orally administered vaccines. Recently, a novel vaccine antigen delivery system, termed virosomes, has been utilized to construct hepatitis A and influenza vaccines. Such vaccines elicit fewer local adverse reactions than their classical counterparts and display enhanced immunogenicity. Virosome-formulated influenza vaccine has also been shown to be safe and immunogenic, when administered by the intranasal route.

Response of Salmonella Typhi to bile-generated oxidative stress: implication of quorum sensing and persister cell populations.

PubMed

Walawalkar, Yogesh D; Vaidya, Yatindra; Nayak, Vijayashree

2016-11-01

Salmonella Typhi can chronically persist within the gallbladder of patients suffering from gallbladder diseases. This study, intended to improve our understanding of bacterial mechanisms underlying bile adaptation, revealed that bile, which is a bactericidal agent, led to the generation of reactive oxygen species in S Typhi. Salmonella Typhi in response showed a significant increase in the production of anti-oxidative enzymes, namely superoxide dismutase and catalase. The work reports that the quorum-sensing (QS) system of S Typhi regulates the level of these enzymes during oxidative stress. In support of these observations, the quorum-sensing mutant of S Typhi was found to be sensitive to bile with significantly lower levels of anti-oxidant enzymes compared to other clinical isolates. Furthermore the addition of exogenous cell-free extracts (CFEs) of S Typhi containing the quorum-sensing signalling molecule significantly increased the levels of these enzymes within the mutant. Interestingly the CFE addition did not significantly restore the biofilm-forming ability of the mutant strain when compared with the wild-type. In the presence of ciprofloxacin and ampicillin, S Typhi formed persister cells which increased >3-fold in the presence of bile. Thus the QS-system of S Typhi aids in oxidative stress management, and enhanced persister cell populations could assist chronic bacterial persistence within the gallbladder. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Acute hepatitis in infectious diseases].

PubMed

Podymova, S D

2013-01-01

Hepatitis A, B, C, D, E, G are the most common causes of acute hepatitis, however, there are many infectious diseases affecting liver and with fever, early diagnostics of which is very important for the clinic of internal diseases. This review presents infections, causing fever and hepatitis, but not necessarily accompanied by jaundice. Leptospirosis, yellow fever have been considered, in which liver damage determines the clinic and the prognosis of the disease. In other cases, such as infectious mononucleosis, cytomegalovirus and herpetic hepatitis, typho-para-typhoid infections, typhoid, pneumonia, some viral diseases, malaria, Legionnaire's disease, hepatitis do not have their independent status and represent one of the important syndromes of a common disease. Modern methods of diagnostics and treatment of these diseases have been described.

Abdominal ultrasonographic findings in typhoid fever: a comparison between typhoid patients and those with non-typhoidal Salmonella and Campylobacter jejuni enterocolitis.

PubMed

Kobayashi, Akira; Adachi, Yasuo; Iwata, Yoshinori; Sakai, Yoshiyuki; Shigemitu, Kazuaki; Todoroki, Miwako; Ide, Mituru

2012-03-01

Typhoid fever is a major health problem in many developing countries and its clinical features are similar to other types of bacterial enterocolitis. Definitive diagnosis by blood culture requires several days and is often unfeasible to perform in developing countries. More efficient and rapid diagnostic methods for typhoid are needed. We compared the pathological changes in the bowel and adjacent tissues of patients having typhoid fever with those having bacterial enterocolitis using ultrasonography. A characteristic of patients with non-typhoidal Salmonella and Campylobacter jejuni enterocolitis was mural thickening of the terminal ileum; only mild mural swelling or no swelling was observed in patients with typhoid fever. Mesenteric lymph nodes in patients with typhoid fever were significantly more enlarged compared to patients with other types of bacterial enterocolitis. Our findings suggest typhoid fever is not fundamentally an enteric disease but rather resembles mesenteric lymphadenopathy and ultrasound is a promising modality for diagnosing typhoid fever in developing countries.

A large and persistent outbreak of typhoid fever caused by consuming contaminated water and street-vended beverages: Kampala, Uganda, January - June 2015.

PubMed

Kabwama, Steven Ndugwa; Bulage, Lilian; Nsubuga, Fred; Pande, Gerald; Oguttu, David Were; Mafigiri, Richardson; Kihembo, Christine; Kwesiga, Benon; Masiira, Ben; Okullo, Allen Eva; Kajumbula, Henry; Matovu, Joseph K B; Makumbi, Issa; Wetaka, Milton; Kasozi, Sam; Kyazze, Simon; Dahlke, Melissa; Hughes, Peter; Sendagala, Juliet Nsimire; Musenero, Monica; Nabukenya, Immaculate; Hill, Vincent R; Mintz, Eric; Routh, Janell; Gómez, Gerardo; Bicknese, Amelia; Zhu, Bao-Ping

2017-01-05

On 6 February 2015, Kampala city authorities alerted the Ugandan Ministry of Health of a "strange disease" that killed one person and sickened dozens. We conducted an epidemiologic investigation to identify the nature of the disease, mode of transmission, and risk factors to inform timely and effective control measures. We defined a suspected case as onset of fever (≥37.5 °C) for more than 3 days with abdominal pain, headache, negative malaria test or failed anti-malaria treatment, and at least 2 of the following: diarrhea, nausea or vomiting, constipation, fatigue. A probable case was defined as a suspected case with a positive TUBEX® TF test. A confirmed case had blood culture yielding Salmonella Typhi. We conducted a case-control study to compare exposures of 33 suspected case-patients and 78 controls, and tested water and juice samples. From 17 February-12 June, we identified 10,230 suspected, 1038 probable, and 51 confirmed cases. Approximately 22.58% (7/31) of case-patients and 2.56% (2/78) of controls drank water sold in small plastic bags (OR M-H  = 8.90; 95%CI = 1.60-49.00); 54.54% (18/33) of case-patients and 19.23% (15/78) of controls consumed locally-made drinks (OR M-H  = 4.60; 95%CI: 1.90-11.00). All isolates were susceptible to ciprofloxacin and ceftriaxone. Water and juice samples exhibited evidence of fecal contamination. Contaminated water and street-vended beverages were likely vehicles of this outbreak. At our recommendation authorities closed unsafe water sources and supplied safe water to affected areas.

Oral and cloacal microflora of wild crocodiles Crocodylus acutus and C. moreletii in the Mexican Caribbean.

PubMed

Charruau, Pierre; Pérez-Flores, Jonathan; Pérez-Juárez, José G; Cedeño-Vázquez, J Rogelio; Rosas-Carmona, Rebeca

2012-02-17

Bacterial cultures and chemical analyses were performed from cloacal and oral swabs taken from 43 American crocodiles Crocodylus acutus and 28 Morelet's crocodiles C. moreletii captured in Quintana Roo State, Mexico. We recovered 47 bacterial species (28 genera and 14 families) from all samples with 51.1% of these belonging to the family Enterobacteriaceae. Fourteen species (29.8%) were detected in both crocodile species and 18 (38.3%) and 15 (31.9%) species were only detected in American and Morelet's crocodiles, respectively. We recovered 35 bacterial species from all oral samples, of which 9 (25.8%) were detected in both crocodile species. From all cloacal samples, we recovered 21 bacterial species, of which 8 (38.1%) were detected in both crocodile species. The most commonly isolated bacteria in cloacal samples were Aeromonas hydrophila and Escherichia coli, whereas in oral samples the most common bacteria were A. hydrophila and Arcanobacterium pyogenes. The bacteria isolated represent a potential threat to crocodile health during conditions of stress and a threat to human health through crocodile bites, crocodile meat consumption or carrying out activities in crocodile habitat. We especially warn about the presence of Salmonella arizonae and S. typhi, which cause enteritis and septicemia in crocodiles and salmonellosis and typhoid fever in humans. The risk of bacterial contamination from crocodiles to humans could increase in the future because of the accelerated destruction of crocodile habitat, which could lead to an augmentation of human-crocodile interactions. Information on bacterial diversity reported here could help in the choice of antibacterial products in case of infections that are of crocodile origin.

THE EFFECT OF IONIZING RADIATION ON THE DEVELOPMENT OF IMMUNITY TO TETANUS AND TYPHOID

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shabarov, I.A.

1958-01-01

The general x-ray irradiation of mice (550 r) 2 days before immunization caused a marked fall in antitoxic (anti-tetanus) and in antibacterial (anti- typhoid) immunity. The immunity developing after the mice had been vaccinated (with 3 injections of tetravalent vaccine and 2 injections of crude toxoid) during a period when they exhibited marked symptoms of radiation sickness was only greater than the natural resistance of nonimmunized healthy mice to injections of tetanus toxin and to infection with typhoid bacilli. When mice were immunized 2 days after general irradiation with purified adsorbed toxoid the immunogenic properties of which greatly exceed thosemore » of ordinary crude toxoid, they exhibited a higher degree of antitoxic immunity than was obtained with ordinary toxoid; however, the difference in the immunological efficacy of these two preparations was less marked in the irradiated animals than in animals which had not been irradiated. (auth)« less

Disease Outbreaks Caused by Water.

ERIC Educational Resources Information Center

Craun, Gunther F.

1978-01-01

Presents a literature review of the disease outbreaks caused by drinking polluted water, covering publications of 1976-77. Some of the waterborn outbreaks included are: (1) cholera; (2) gastroenteritis; (3) giardiasis; and (4) typhoid fever and salmonellosis. A list of 66 references is also presented. (HM)

The plague of Athens: epidemiology and paleopathology.

PubMed

Littman, Robert J

2009-10-01

In 430 BC, a plague struck the city of Athens, which was then under siege by Sparta during the Peloponnesian War (431-404 BC). In the next 3 years, most of the population was infected, and perhaps as many as 75,000 to 100,000 people, 25% of the city's population, died. The Athenian general and historian Thucydides left an eye-witness account of this plague and a detailed description to allow future generations to identify the disease should it break out again. Because of the importance of Thucydides and Athens in Western history and culture, the Plague of Athens has taken a prominent position in the history of the West for the past 2500 years. Despite Thucydides' careful description, in the past 100 years, scholars and physicians have disagreed about the identification of the disease. Based on clinical symptoms, 2 diagnoses have dominated the modern literature on the Athenian plague: smallpox and typhus. New methodologies, including forensic anthropology, demography, epidemiology, and paleopathogy, including DNA analysis, have shed new light on the problem. Mathematical modeling has allowed the examination of the infection and attack rates and the determination of how long it takes a disease to spread in a city and how long it remains endemic. The highly contagious epidemic exhibited a pustular rash, high fever, and diarrhea. Originating in Ethiopia, it spread throughout the Mediterranean. It spared no segment of the population, including the statesman Pericles. The epidemic broke in early May 430 BC, with another wave in the summer of 428 BC and in the winter of 427-426 BC, and lasted 4.5 to 5 years. Thucydides portrays a virgin soil epidemic with a high attack rate and an unvarying course in persons of different ages, sexes, and nationalities.The epidemiological analysis excludes common source diseases and most respiratory diseases. The plague can be limited to either a reservoir diseases (zoonotic or vector-borne) or one of the respiratory diseases associated with an unusual means of persistence, either environmental/fomite persistence or adaptation to indolent transmission among dispersed rural populations. The first category includes typhus, arboviral diseases, and plague, and the second category includes smallpox. Both measles and explosive streptococcal disease appear to be much less likely candidates.In 2001, a mass grave was discovered that belonged to the plague years. Ancient microbial typhoid (Salmonella enterica serovar Typhi) DNA was extracted from 3 skeletons. Because typhoid was endemic in the Greek world, it is not the likely cause of this sudden epidemic. Mt Sinai J Med 76:456-467, 2009. (c) 2009 Mount Sinai School of Medicine.

Medicinal plants of the genus Anthocleista--A review of their ethnobotany, phytochemistry and pharmacology.

PubMed

Anyanwu, Gabriel O; Nisar-ur-Rehman; Onyeneke, Chukwu E; Rauf, Khalid

2015-12-04

The genus Anthocleista of the Gentianaceae family contains 14 species of trees and shrub-like plants distributed in tropical Africa, in Madagascar and on the Comoros. Traditionally, they are commonly used in the treatment of diabetes, hypertension, malaria, typhoid fever, obesity, diarrhea, dysentery, hyperprolactinemia, abdominal pain, ulcer, jaundice, asthma, hemorrhoids, hernia, cancer, wounds, chest pains, inflammations, rheumatism, STDs, infertility and skin diseases. They serve as an anthelmintic, laxative, diuretic and contraceptive. This review aims to provide for the first time a repository of ethnopharmacological information while critically evaluating the relation between the traditional medicinal uses, chemical constituents and pharmacological activities of the Anthocleista species so as to unveil opportunities for future research. A search for relevant information on Anthocleista species was performed on scientific databases (Pubmed, Google Scholar, SciFinder, Web of Science, Scopus, PubChem and other web sources such as The Plant List, Kew Botanical Garden and PROTA) and books, PhD and MSc dissertations for un-published resources. Out of the 14 species of Anthocleista, 6 have been reported in literature to be widely used in traditional medicine for the treatment of various ailments. The six species include: A. djalonensis, A. vogelii, A. nobilis, A. grandiflora, A. schweinfurthii, and A. liebrechtsiana. The chemical compounds isolated from Anthocleista species fall into the class of phytochemicals such as secoiridoids, nor-secoiridoids, xanthones, phytosterols, triterpenes, alkaloids, and others of which majority of the compounds were isolated from A. djalonensis and A. vogelii. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Anthocleista species showed antidiabetic, antiplasmodial, antimicrobial, hypotensive, spasmogenic, anti-obesity, antiulcerogenic, analgesic, anti-inflammatory, antioxidant, antitrypanosomal, anthelmintic, fertility, diuretic and laxative activities which supports most of their uses in traditional medicine. However, the bulk of the studies where centered on the antidiabetic, antiplasmodial and antimicrobial activities of Anthocleista species, although the evidence of its antiplasmodial effect was not convincing enough due to the discrepancies between the in vitro and in vivo results. A. djalonensis and A. vogelii are potential antidiabetic and antibacterial agents. The antibacterial potency relates to infections or diseases caused by E. coli, S. typhi and S. aureus such as urinary tract infections, typhoid, diarrhea, skin diseases, and food poisoning. Pharmacological research on this genus is quite elementary and limited, thus, more advanced research is necessary to isolate and determine the activities of bioactive compounds in vitro and in vivo, establish their mechanisms of action and commence the process of clinical research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Multiplex quantification of Escherichia coli, Salmonella typhi and Vibrio cholera with three DNA targets in single reaction assay.

PubMed

Jangampalli Adi, Pradeepkiran; Naidu, Jagadish R; Matcha, Bhaskar

2017-09-01

Escherichia coli (E. coli), Salmonella typhi and Vibrio cholera harmful pathogens, which causes various diseases in humans. Rapid diagnosis of bacterial infection is an important for patient management and appropriate therapy during the early phase of the bacterial infected diseases. Among the existing techniques for identifying pathogens were less sensitive and time-consuming processes. In the present study total, 48 clinical 31 blood and 17 urine samples of patients suspected with the infections were collected from SVRR Hospital and used to detect the pathogens. Multiplex polymerase chain reaction (PCR) assay was set to design for the identification of Escherichia coli, Salmonella typhi and Vibrio cholera from the different clinical samples. Rapid diagnosis of Escherichia coli (E. coli), Salmonella and Vibrio cholera pathogens can be done with simultaneously in a single multiplex PCR assay by using specific primers with adjusted PCR conditions. Through this approach, the results represented with out of 31 blood samples 1-15 shows the positive with E. coli and remaining 14 only 11 were correlated with multiplex results of Vibrio cholera, remaining the urine samples all are positive with 17 samples correlate with the Salmonella typhi. Through the high specificity benefits of excellent sensitivity, with high resolution and reproducibility. This method of results proved and illustrates the best potential system for diagnosing the infectious disease with modern trendy. Copyright © 2017 Elsevier Ltd. All rights reserved.

The prevalence and clinical features of multi-drug resistant Salmonella typhi infections in Baluchistan, Pakistan.

PubMed

Mirza, S H; Beeching, N J; Hart, C A

1995-10-01

Between January and July 1994, a prospective study of bacteraemia in 692 patients with fever without localizing signs was undertaken at the Quetta Military Hospital in Baluchistan, Pakistan. Salmonella spp. were isolated from 76 (11%) of the patients; 62 had S. typhi and 14 had S. paratyphi A. Significantly more isolations of S. typhi were made in the hot dry months of May and June than in the earlier months. Although multi-drug resistance (to chloramphenicol ampicillin and cotrimoxazole) was detected in 43 (69%) of the S. typhi isolates, it was not found in any of the S. paratyphi A. Defervescence of patients with chloramphenicol-sensitive S. typhi took 7-10 days of chloramphenicol therapy. In contrast, most (91%) of the patients infected with multi-drug resistant S. typhi who were treated with fluoroquinolones achieved defervescence in 1-3 days; the remainder took 4-6 days.

Salmonella Infections

MedlinePlus

... reptiles like snakes, turtles, and lizards. Symptoms include Fever Diarrhea Abdominal cramps Headache Possible nausea, vomiting, and ... be serious. The usual treatment is antibiotics. Typhoid fever, a more serious disease caused by Salmonella, is ...

THE EFFICACY OF REVACCINATION AGAINST TYPHOID FEVER IN IRRADIATED ANIMALS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tumanyan, M.A.; Izvekova, A.V.

1958-01-01

It was shown in the previous work that an exposure to x radiation after immunization considerably decreases the immunity of animals to typhoid fever infection. It is now shown that revaccination carried out in 10 days following irradiation causes pronounced immunity in irradiated white mice, which is not less than the immunity of revaccinated animals not subjected to irradation. Production of immunity in revaccinated animals is due to the changes of immunological reactivity which is preserved in the irradiated organism and appears as a result of primary immunization, carried out before the irradiation. (tr-auth)

21 CFR 520.2325a - Sulfaquinoxaline drinking water.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Chickens. (i) As an aid in the control of outbreaks of coccidiosis caused by Eimeria tenella, E. necatrix... not change litter unless absolutely necessary. Do not give flushing mashes. (3) Chickens and turkeys... sulfaquinoxaline and fowl typhoid caused by Salmonella gallinarum susceptible to sulfaquinoxaline. (ii) Administer...

21 CFR 520.2325a - Sulfaquinoxaline drinking water.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Chickens. (i) As an aid in the control of outbreaks of coccidiosis caused by Eimeria tenella, E. necatrix... not change litter unless absolutely necessary. Do not give flushing mashes. (3) Chickens and turkeys... sulfaquinoxaline and fowl typhoid caused by Salmonella gallinarum susceptible to sulfaquinoxaline. (ii) Administer...

21 CFR 520.2325a - Sulfaquinoxaline drinking water.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Chickens. (i) As an aid in the control of outbreaks of coccidiosis caused by Eimeria tenella, E. necatrix... not change litter unless absolutely necessary. Do not give flushing mashes. (3) Chickens and turkeys... sulfaquinoxaline and fowl typhoid caused by Salmonella gallinarum susceptible to sulfaquinoxaline. (ii) Administer...

Liver Necrosis and Lethal Systemic Inflammation in a Murine Model of Rickettsia typhi Infection: Role of Neutrophils, Macrophages and NK Cells.

PubMed

Papp, Stefanie; Moderzynski, Kristin; Rauch, Jessica; Heine, Liza; Kuehl, Svenja; Richardt, Ulricke; Mueller, Heidelinde; Fleischer, Bernhard; Osterloh, Anke

2016-08-01

Rickettsia (R.) typhi is the causative agent of endemic typhus, an emerging febrile disease that is associated with complications such as pneumonia, encephalitis and liver dysfunction. To elucidate how innate immune mechanisms contribute to defense and pathology we here analyzed R. typhi infection of CB17 SCID mice that are congenic to BALB/c mice but lack adaptive immunity. CB17 SCID mice succumbed to R. typhi infection within 21 days and showed high bacterial load in spleen, brain, lung, and liver. Most evident pathological changes in R. typhi-infected CB17 SCID mice were massive liver necrosis and splenomegaly due to the disproportionate accumulation of neutrophils and macrophages (MΦ). Both neutrophils and MΦ infiltrated the liver and harbored R. typhi. Both cell populations expressed iNOS and produced reactive oxygen species (ROS) and, thus, exhibited an inflammatory and bactericidal phenotype. Surprisingly, depletion of neutrophils completely prevented liver necrosis but neither altered bacterial load nor protected CB17 SCID mice from death. Furthermore, the absence of neutrophils had no impact on the overwhelming systemic inflammatory response in these mice. This response was predominantly driven by activated MΦ and NK cells both of which expressed IFNγ and is considered as the reason of death. Finally, we observed that iNOS expression by MΦ and neutrophils did not correlate with R. typhi uptake in vivo. Moreover, we demonstrate that MΦ hardly respond to R. typhi in vitro. These findings indicate that R. typhi enters MΦ and also neutrophils unrecognized and that activation of these cells is mediated by other mechanisms in the context of tissue damage in vivo.

Summary of the Statement on International Travellers and Typhoid by the Committee to Advise on Tropical Medicine and Travel (CATMAT)

PubMed Central

Greenaway, C; Schofield, S; Henteleff, A; Plourde, P; Geduld, J; Abdel-Motagally, M; Bryson, M

2014-01-01

Background Typhoid fever is an enteric febrile illness with symptoms that range from mild to potentially fatal. Among Canadians it is usually acquired during travel to typhoid endemic countries. The Committee to Advise on Tropical Medicine and Travel (CATMAT) assembled a typhoid working group to update recommendations on typhoid and international travel. This document is a summary of the new typhoid statement. Methods Following a systematic review of the literature, typhoid vaccine recommendations were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to evaluate data quality, benefits and harms, and values and preferences. The literature search focused on systematic reviews of typhoid vaccine efficacy and identified studies of disease burden, pathogenesis, risk factors and prevention. Other recommendations were based on a review of the retrieved literature and expert opinion. Results Typhoid vaccine is moderately effective (~50%), well tolerated, with very low risk of serious adverse events. Studies of typhoid vaccine efficacy, morbidity or mortality among travellers were not found, although studies on populations in typhoid endemic countries were identified. Among travellers, destination of travel is the strongest and most consistent typhoid risk predictor; the highest risk was for travel to South Asia. Confidence in effect estimates for other potential risk factors was very low. Recommendations CATMAT suggests that typhoid vaccine (Ty21a or Vi polysaccharide vaccine) be used for most Canadian travellers visiting South Asia and not used for most Canadian travellers visiting destinations other than South Asia. The recommendations are conditional, due to the moderate confidence in the effect estimate. For destinations other than South Asia, providers should discuss risks and vaccine benefits and harms with the traveller as well as recommend basic hygiene precautions.

Development of a one-step immunochromatographic strip test using gold nanoparticles for the rapid detection of Salmonella typhi in human serum.

PubMed

Preechakasedkit, Pattarachaya; Pinwattana, Kulwadee; Dungchai, Wijitar; Siangproh, Weena; Chaicumpa, Wanpen; Tongtawe, Pongsri; Chailapakul, Orawon

2012-01-15

An immunochromatographic strip test using gold nanoparticles was developed for the rapid detection of Salmonella typhi (S. typhi) in human serum. The strip test based on the principle of sandwich immunoassay by the specific binding of antigens from S. typhi O901 and antibody of S. typhi O901 on a nitrocellulose membrane. Antibody-gold nanoparticle conjugate was used as the label and was coated onto a glass fiber membrane, which was used as a conjugate pad. To create a test and control zone, antibody of S. typhi O901 and an anti-IgG were dotted on the nitrocellulose membrane, respectively. Positive samples were displayed as red dots at the test and control zones of the nitrocellulose membrane, while negative samples resulted in a red dot only in the control zone. The limit of detection (LOD) was found to be 1.14×10(5) cfu mL(-1), which could be visually detected by the naked eye within 15 min. This strip test provided a lower detection limit and analysis time than a dot blot immunoassay (8.88×10(6) cfu mL(-1) for LOD and 110 min for reaction time). In addition, our immunochromatographic strip test was employed to detect S. typhi in human serum effectively, with high accuracy. This strip test offers great promise for a rapid, simple and low-cost analysis of S. typhi. Copyright © 2011 Elsevier B.V. All rights reserved.

Burden of typhoid fever in Sulaimania, Iraqi Kurdistan.

PubMed

Dworkin, Jonathan; Saeed, Rebeen; Mykhan, Hawar; Kanan, Shwan; Farhad, Dlawer; Ali, Kocher Omer; Abdulwahab, Runak Hama Kareem; Palardy, John; Neill, Marguerite A

2014-10-01

Typhoid fever imposes a high disease burden worldwide, but resource limitations mean that the burden of typhoid fever in many countries is poorly understood. The authors conducted a prospective surveillance study at the adult and pediatric teaching hospitals in Sulaimania, Iraqi Kurdistan. All patients presenting with an undifferentiated febrile illness consistent with typhoid were eligible for enrollment. Enrolled patients had blood cultures and Brucella serologies performed. Incidence was calculated with reference to census data. Both typhoid fever and brucellosis were common, and the incidence of typhoid fever was 21 cases/100 000 patient-years. Classic disease symptoms were uncommonly observed. Cost-effective surveillance projects to calculate disease burden of typhoid fever are practical and replicable. Typhoid has successfully adapted to the healthcare environment in Sulaimania. Additional work in the region should focus on antibiotic resistance and other enteric pathogens such as Brucella spp. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Antimicrobial sensitivity pattern of Salmonella: comparison of isolates from HIV-infected and HIV-uninfected patients.

PubMed

Wolday, D; Erge, W

1998-07-01

A retrospective analysis of all cases of Salmonella infections occurring between 1991 and 1995 was undertaken in order to evaluate the antimicrobial sensitivity pattern of the isolates from both human immunodeficiency virus (HIV) infected and uninfected Ethiopian patients. During the 5-year study period, we identified 147 cases of Salmonella infections. Only in 49 cases was the HIV serostatus known; 22 (44.9%) of the infections were in HIV seronegative patients while 27 (55.9%) were in HIV seropositive patients. The strains were isolated from blood (71.4%), urine (18.4%) and stool (8.2%). Salmonella infection was found to be more frequent (55.15% versus 44.9%) among HIV positive than HIV-negative patients. Moreover, Salmonella isolates recovered from HIV-seropositive patients were significantly resistant to many of the antibiotics tested when compared to the isolates from HIV-seronegative patients. The only chloramphenicol resistant Salmonella typhi occurred in a patient who was seropositive for HIV. According to these results, Ethiopian patients infected with HIV may be at risk of acquiring infections, especially non-typhoidal salmonellas, that are multi-drug resistant (MDR) strains than HIV-uninfected subjects. The emergence of MDR Salmonella infection among HIV-positive patients requires reassessment of chemotherapeutic approaches in this patient population, and warrants continued laboratory surveillance.

Utilization of plant-derived recombinant human β-defensins (hBD-1 and hBD-2) for averting salmonellosis.

PubMed

Patro, Sunita; Maiti, Soumitra; Panda, Santosh Kumar; Dey, Nrisingha

2015-04-01

We describe the use of plant-made β-defensins as effective antimicrobial substances for controlling salmonellosis, a deadly infection caused by Salmonella typhimurium (referred to further as S. typhi). Human β-defensin-1 (hBD-1) and -2 (hBD-2) were expressed under the control of strong constitutive promoters in tobacco plants, and bio-active β-defensins were successfully extracted. In the in vitro studies, enriched recombinant plant-derived human β-defensin-1 (phBD-1) and -2 (phBD-2) obtained from both T1 and T2 transgenic plants showed significant antimicrobial activity against Escherichia coli and S. typhi when used individually and in various combinations. The 2:1 peptide combination of phBD-1:phBD-2 with peptides isolated from T1-and T2-generation plants reduced the growth of S. typhi by 96 and 85 %, respectively. In vivo studies employing the mouse model (Balb/c) of Salmonella infection clearly demonstrated that the administration of plant-derived defensins individually and in different combinations enhanced the mean survival time of Salmonella-infected animals. When treatment consisted of the 2:1 phBD-1:phBD-2 combination, approximately 50 % of the infected mice were still alive at 206 h post-inoculation; the lowest number of viable S. typhi was observed in the liver and spleen of infected animals. We conclude that plant-made recombinant β-defensins (phBD-1 and phBD-2) are promising antimicrobial substances and have the potential to become additional tools against salmonellosis, particularly when used in combination.

The influence of MAP condition and active compounds on the radiosensitization of Escherichia coli and Salmonella typhi present in chicken breast

NASA Astrophysics Data System (ADS)

Lacroix, M.; Chiasson, F.

2004-09-01

The efficiency of carvacrol, thymol, trans-cinnamaldehyde (Tc) and tetrasodium pyrophosphate (Tp) on the radiosensitization of Escherichia coli and Salmonella typhi in chicken breast was determined. Chicken breast were dipped in a bath of working cultures of E. coli or S. typhi (5×10 7 CFU/ml). Active compounds were added at the concentration corresponding to {1}/{30} of the minimal inhibitory concentration. Samples were packed under air and gamma irradiation was done at doses from 0.1 to 0.7 kGy. The efficiencies of the active compounds against E. coli were 32%, 10%, 3% and 0% for thymol, Tp and carvacrol, respectively. For S. typhi, the efficiencies in the chicken breast were 47%, 19%, 17% and 11% for Tc, Tp, carvacrol and thymol, respectively. Without active compounds, D10 values were 0.145 kGy for E. coli and 0.64 kGy for S. typhi as compared to 0.098 kGy for E. coli and 0.341 kGy for S. typhi in presence of Tc. Under modified atmospheric packaging condition and in presence of Tc, D10 values were reduced to 0.046 for E. coli and to 0.110 for S. typhi.

Dengue and Other Common Causes of Acute Febrile Illness in Asia: An Active Surveillance Study in Children

PubMed Central

Capeding, Maria Rosario; Chua, Mary Noreen; Hadinegoro, Sri Rezeki; Hussain, Ismail I. H. M.; Nallusamy, Revathy; Pitisuttithum, Punnee; Rusmil, Kusnandi; Thisyakorn, Usa; Thomas, Stephen J.; Huu Tran, Ngoc; Wirawan, Dewa Nyoman; Yoon, In-Kyu; Bouckenooghe, Alain; Hutagalung, Yanee; Laot, Thelma; Wartel, Tram Anh

2013-01-01

Background Common causes of acute febrile illness in tropical countries have similar symptoms, which often mimic those of dengue. Accurate clinical diagnosis can be difficult without laboratory confirmation and disease burden is generally under-reported. Accurate, population-based, laboratory-confirmed incidence data on dengue and other causes of acute fever in dengue-endemic Asian countries are needed. Methods and principal findings This prospective, multicenter, active fever surveillance, cohort study was conducted in selected centers in Indonesia, Malaysia, Philippines, Thailand and Vietnam to determine the incidence density of acute febrile episodes (≥38°C for ≥2 days) in 1,500 healthy children aged 2–14 years, followed for a mean 237 days. Causes of fever were assessed by testing acute and convalescent sera from febrile participants for dengue, chikungunya, hepatitis A, influenza A, leptospirosis, rickettsia, and Salmonella Typhi. Overall, 289 participants had acute fever, an incidence density of 33.6 per 100 person-years (95% CI: 30.0; 37.8); 57% were IgM-positive for at least one of these diseases. The most common causes of fever by IgM ELISA were chikungunya (in 35.0% of in febrile participants) and S. Typhi (in 29.4%). The overall incidence density of dengue per 100 person-years was 3.4 by nonstructural protein 1 (NS1) antigen positivity (95% CI: 2.4; 4.8) and 7.3 (95% CI: 5.7; 9.2) by serology. Dengue was diagnosed in 11.4% (95% CI: 8.0; 15.7) and 23.9% (95% CI: 19.1; 29.2) of febrile participants by NS1 positivity and serology, respectively. Of the febrile episodes not clinically diagnosed as dengue, 5.3% were dengue-positive by NS1 antigen testing and 16.0% were dengue-positive by serology. Conclusions During the study period, the most common identified causes of pediatric acute febrile illness among the seven tested for were chikungunya, S. Typhi and dengue. Not all dengue cases were clinically diagnosed; laboratory confirmation is essential to refine disease burden estimates. PMID:23936565

Salmonella serotypeTyphi, Shigella, and intestinal parasites among food handlers at Bahir Dar University, Ethiopia.

PubMed

Abera, Bayeh; Yitayew, Gashaw; Amare, Hiwot

2016-02-28

Food handlers play a major role in the transmission of Salmonella serotype Typhi (S. Typhi), Shigella, and intestinal parasites. This study was conducted to determine the prevalence of S. Typhi, Shigella, and intestinal parasites among food handlers at Bahir Dar University, Ethiopia. A cross-sectional study was conducted in June 2014. Stool samples from 410 food handlers were examined for bacterial pathogens and parasites. Pearson's Chi-square test, Fisher's exact test, and bivariate and multivariate logistic regression analyses were used where appropriate. The prevalence of S. Typhi, Shigella, and intestinal parasites among food handlers was 11 (2.7%), 5 (1.2%), and 53 (12.9%), respectively. Among eight intestinal parasites identified, the two most prevalent intestinal parasites were hookworm 26 (6.3%) and G. lamblia 13 (3.1%). Male food handlers were more likely to be positive than were female food handlers for S. Typhi and intestinal parasites. Furthermore, food handlers who had a history of regular medical checkups were less infected with intestinal parasites. Being male (AOR: 2.1, 95% CI: 1.2, 4.4) and not attending medical checkups (AOR: 2.9, 95% CI: 1.4, 6.1) were independent predictors of intestinal parasitic infection in food handlers. Male food handlers were reluctant to have regular parasitological examinations. There was a high proportion of food handlers with S. Typhi, Shigella, and intestinal parasites in their faces. Special emphasis should be placed on S. Typhicarriers and male food handlers. Education and periodical medical checkups for intestinal parasites and S. Typhi should be considered as intervention measures.

Characterization of the type I dehydroquinase from Salmonella typhi.

PubMed Central

Moore, J D; Hawkins, A R; Charles, I G; Deka, R; Coggins, J R; Cooper, A; Kelly, S M; Price, N C

1993-01-01

The type I dehydroquinase from the human pathogen Salmonella typhi was overexpressed in an Escherichia coli host and purified to homogeneity. The S. typhi enzyme was characterized in terms of its kinetic parameters, important active-site residues, thermal stability and c.d. and fluorescence properties. In all important respects, the enzyme from S. typhi behaves in a very similar fashion to the well-characterized enzyme from E. coli, including the remarkable conformational stabilization observed on reduction of the substrate/product mixture by NaBH4. This gives confidence that the information from X-ray studies on the S. typhi enzyme [Boys, Fawcett, Sawyer, Moore, Charles, Hawkins, Deka, Kleanthous and Coggins (1992) J. Mol. Biol. 227, 352-355] can be applied to other type I dehydroquinases. Studies of the quenching of fluorescence of the S. typhi enzyme by succinimide show that NaBH4 reduction of the substrate/product imine complex involves a dramatic decrease in the flexibility of the enzyme, with only very minor changes in the overall secondary and tertiary structure. Images Figure 1 PMID:8216229

Identification and Characterization of a Cis Antisense RNA of the rpoH Gene of Salmonella enterica Serovar Typhi.

PubMed

Xiong, Changyan; Li, Xuejiao; Liu, Juanli; Zhao, Xin; Xu, Shungao; Huang, Xinxiang

2018-01-01

Antisense RNAs from complementary strands of protein coding genes regulate the expression of genes involved in many cellular processes. Using deep sequencing analysis of the Salmonella enterica serovar Typhi ( S. Typhi) transcriptome, a novel antisense RNA encoded on the strand complementary to the rpoH gene was revealed. In this study, the molecular features of this antisense RNA were assessed using northern blotting and rapid amplification of cDNA ends. The 3,508 nt sequence of RNA was identified as the antisense RNA of the rpoH gene and was named ArpH. ArpH was found to attenuate the invasion of HeLa cells by S. Typhi by regulating the expression of SPI-1 genes. In an rpoH mutant strain, the invasive capacity of S. Typhi was increased, whereas overexpression of ArpH positively regulates rpoH mRNA levels. Results of this study suggest that the cis -encoded antisense RNA ArpH is likely to affect the invasive capacity of S. Typhi by regulating the expression of rpoH .

Spectrum of perforation peritonitis in delhi: 77 cases experience.

PubMed

Yadav, Dinesh; Garg, Puneet K

2013-04-01

Perforation peritonitis is the most common surgical emergency encountered by surgeons all over the world as well in India. The spectrum of etiology of perforation peritonitis in tropical countries continues to differ from its western counterpart. This study was conducted at Hindu Rao Hospital, Municipal Corporation of Delhi, New Delhi, India, designed to highlight the spectrum of perforation peritonitis in the eastern countries and to improve its outcome. This prospective study included 77 consecutive patients of perforation peritonitis studied in terms of clinical presentations, causes, site of perforation, surgical treatment, postoperative complications, and mortality at Hindu Rao Hospital, Delhi, from March 1, 2011 to December 1, 2011, over a period of 8 months. All patients were resuscitated and underwent emergency exploratory laparotomy. On laparotomy cause of perforation peritonitis was found and controlled. The most common cause of perforation peritonitis noticed in our series was perforated duodenal ulcer (26.4 %) and ileal typhoid perforation (26.4 %), each followed by small bowel tuberculosis (10.3 %) and stomach perforation (9.2 %), perforation due to acute appendicitis (5 %). The highest number of perforations was seen in ileum (39.1 %), duodenum (26.4 %), stomach (11.5 %), appendix (3.5 %), jejunum (4.6 %), and colon (3.5 %). Overall mortality was 13 %. The spectrum of perforation peritonitis in India continuously differs from western countries. The highest number of perforations was noticed in the upper part of the gastrointestinal tract as compared to the western countries where the perforations seen mostly in the distal part. The most common cause of perforation peritonitis was perforated duodenal ulcer and small bowel typhoid perforation followed by typhoid perforation. Large bowel perforations and malignant perforations were least common in our setup.

Typhoid Fever in nineteenth-century Colombia: between medical geography and bacteriology.

PubMed

García, Mónica

2014-01-01

This paper analyses how the Colombian medical elites made sense of typhoid fever before and during the inception of bacteriological ideas and practices in the second half of the nineteenth century. Assuming that the identity of typhoid fever has to be understood within the broader concerns of the medical community in question, I show how doctors first identified Bogotá's epidemics as typhoid fever during the 1850s, and how they also attached specificity to the fever amongst other continuous fevers, such as its European and North American counterparts. I also found that, in contrast with the discussions amongst their colleagues from other countries, debates about typhoid fever in 1860-70 among doctors in Colombia were framed within the medico-geographical scheme and strongly shaped by the fear of typhoid fever appearing alongside 'paludic' fevers in the highlands. By arguing in medico-geographical and clinical terms that typhoid fever had specificity in Colombia, and by denying the medico-geographical law of antagonism between typhoid and paludic fevers proposed by the Frenchman Charles Boudin, Colombian doctors managed to question European knowledge and claimed that typhoid fever had distinct features in Colombia. The focus on paludic and typhoid fevers in the highlands might explain why the bacteriological aetiology of typhoid fever was ignored and even contested during the 1880s. Anti-Pasteurian arguments were raised against its germ identity and some physicians even supported the idea of spontaneous origin of the disease. By the 1890s, Pasteurian knowledge had come to shape clinical and hygienic practices.

A 3' UTR-derived non-coding RNA RibS increases expression of cfa and promotes biofilm formation of Salmonella enterica serovar Typhi.

PubMed

Zhao, Xin; Liu, Rui; Tang, Hao; Osei-Adjei, George; Xu, Shungao; Zhang, Ying; Huang, Xinxiang

2018-05-08

Bacterial non-coding RNAs (ncRNAs) are widely studied and found to play important roles in regulating various cellular processes. Recently, many ncRNAs have been discovered to be transcribed or processed from 3' untranslated regions (3' UTRs). Here we reported a novel 3' UTR-derived ncRNA, RibS, which could influence biofilm formation of Salmonella enterica serovar Typhi (S. Typhi). RibS was confirmed to be a ∼700 nt processed product produced by RNase III-catalyzed cleavage from the 3' UTR of riboflavin synthase subunit alpha mRNA, RibE. Overexpression of RibS increased the expression of the cyclopropane fatty acid synthase gene, cfa, which was located at the antisense strand. Biofilm formation of S. Typhi was enhanced by overexpressing RibS both in the wild type strain and cfa deletion mutant. Deletion of cfa attenuated biofilm formation of S. Typhi, while complementation of cfa partly restored the phenotype. Moreover, overexpressing cfa enhanced the biofilm formation of S. Typhi. In summary, RibS has been identified as a novel ncRNA derived from the 3' UTR of RibE that promotes biofilm formation of S. Typhi, and it appears to do so, at least in part, by increasing the expression of cfa. Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

A Case Report of Salmonella muenchen Enteritis Causing Rhabdomyolysis and Myocarditis in a Previously Healthy 26-Year-Old Man.

PubMed

Chapple, Will; Martell, Jon; Wilson, Joy S; Matsuura, Don T

2017-04-01

This case report examines an unusual presentation of a non-typhoidal Salmonella serovar with limited prevalence in the literature. This is the first case report to associate specifically the Salmonella muenchen serovar with rhabdomyolysis and myocarditis. This case report reviews the diagnostic criteria for myocarditis and explores the diagnostic dilemma of troponin elevation in the setting of rhabdomyolysis. It demonstrates that Salmonella muenchen has the ability to present in a broad range of individuals with complications extending beyond classical gastrointestinal symptoms. This report also concludes that diagnosis of the many possible complications from non-typhoidal Salmonella infections can be difficult due to patient comorbidities, variability in the severity of the illnesses, laboratory test limitations, and imaging limitations. When a patient presents with elevated troponins in the setting of rhabdomyolysis a careful workup should be done to evaluate for ischemic causes, myocarditis, or false elevation secondary to rhabdomyolysis.

Upgrading a Piped Water Supply from Intermittent to Continuous Delivery and Association with Waterborne Illness: A Matched Cohort Study in Urban India

PubMed Central

Ercumen, Ayse; Arnold, Benjamin F.; Kumpel, Emily; Burt, Zachary; Ray, Isha; Nelson, Kara; Colford, John M.

2015-01-01

Background Intermittent delivery of piped water can lead to waterborne illness through contamination in the pipelines or during household storage, use of unsafe water sources during intermittencies, and limited water availability for hygiene. We assessed the association between continuous versus intermittent water supply and waterborne diseases, child mortality, and weight for age in Hubli-Dharwad, India. Methods and Findings We conducted a matched cohort study with multivariate matching to identify intermittent and continuous supply areas with comparable characteristics in Hubli-Dharwad. We followed 3,922 households in 16 neighborhoods with children <5 y old, with four longitudinal visits over 15 mo (Nov 2010–Feb 2012) to record caregiver-reported health outcomes (diarrhea, highly credible gastrointestinal illness, bloody diarrhea, typhoid fever, cholera, hepatitis, and deaths of children <2 y old) and, at the final visit, to measure weight for age for children <5 y old. We also collected caregiver-reported data on negative control outcomes (cough/cold and scrapes/bruises) to assess potential bias from residual confounding or differential measurement error. Continuous supply had no significant overall association with diarrhea (prevalence ratio [PR] = 0.93, 95% confidence interval [CI]: 0.83–1.04, p = 0.19), bloody diarrhea (PR = 0.78, 95% CI: 0.60–1.01, p = 0.06), or weight-for-age z-scores (Δz = 0.01, 95% CI: −0.07–0.09, p = 0.79) in children <5 y old. In prespecified subgroup analyses by socioeconomic status, children <5 y old in lower-income continuous supply households had 37% lower prevalence of bloody diarrhea (PR = 0.63, 95% CI: 0.46–0.87, p-value for interaction = 0.03) than lower-income intermittent supply households; in higher-income households, there was no significant association between continuous versus intermittent supply and child diarrheal illnesses. Continuous supply areas also had 42% fewer households with ≥1 reported case of typhoid fever (cumulative incidence ratio [CIR] = 0.58, 95% CI: 0.41–0.78, p = 0.001) than intermittent supply areas. There was no significant association with hepatitis, cholera, or mortality of children <2 y old; however, our results were indicative of lower mortality of children <2 y old (CIR = 0.51, 95% CI: 0.22–1.07, p = 0.10) in continuous supply areas. The major limitations of our study were the potential for unmeasured confounding given the observational design and measurement bias from differential reporting of health symptoms given the nonblinded treatment. However, there was no significant difference in the prevalence of the negative control outcomes between study groups that would suggest undetected confounding or measurement bias. Conclusions Continuous water supply had no significant overall association with diarrheal disease or ponderal growth in children <5 y old in Hubli-Dharwad; this might be due to point-of-use water contamination from continuing household storage and exposure to diarrheagenic pathogens through nonwaterborne routes. Continuous supply was associated with lower prevalence of dysentery in children in low-income households and lower typhoid fever incidence, suggesting that intermittently operated piped water systems are a significant transmission mechanism for Salmonella typhi and dysentery-causing pathogens in this urban population, despite centralized water treatment. Continuous supply was associated with reduced transmission, especially in the poorer higher-risk segments of the population. PMID:26505897

Upgrading a piped water supply from intermittent to continuous delivery and association with waterborne illness: a matched cohort study in urban India.

PubMed

Ercumen, Ayse; Arnold, Benjamin F; Kumpel, Emily; Burt, Zachary; Ray, Isha; Nelson, Kara; Colford, John M

2015-10-01

Intermittent delivery of piped water can lead to waterborne illness through contamination in the pipelines or during household storage, use of unsafe water sources during intermittencies, and limited water availability for hygiene. We assessed the association between continuous versus intermittent water supply and waterborne diseases, child mortality, and weight for age in Hubli-Dharwad, India. We conducted a matched cohort study with multivariate matching to identify intermittent and continuous supply areas with comparable characteristics in Hubli-Dharwad. We followed 3,922 households in 16 neighborhoods with children <5 y old, with four longitudinal visits over 15 mo (Nov 2010-Feb 2012) to record caregiver-reported health outcomes (diarrhea, highly credible gastrointestinal illness, bloody diarrhea, typhoid fever, cholera, hepatitis, and deaths of children <2 y old) and, at the final visit, to measure weight for age for children <5 y old. We also collected caregiver-reported data on negative control outcomes (cough/cold and scrapes/bruises) to assess potential bias from residual confounding or differential measurement error. Continuous supply had no significant overall association with diarrhea (prevalence ratio [PR] = 0.93, 95% confidence interval [CI]: 0.83-1.04, p = 0.19), bloody diarrhea (PR = 0.78, 95% CI: 0.60-1.01, p = 0.06), or weight-for-age z-scores (Δz = 0.01, 95% CI: -0.07-0.09, p = 0.79) in children <5 y old. In prespecified subgroup analyses by socioeconomic status, children <5 y old in lower-income continuous supply households had 37% lower prevalence of bloody diarrhea (PR = 0.63, 95% CI: 0.46-0.87, p-value for interaction = 0.03) than lower-income intermittent supply households; in higher-income households, there was no significant association between continuous versus intermittent supply and child diarrheal illnesses. Continuous supply areas also had 42% fewer households with ≥1 reported case of typhoid fever (cumulative incidence ratio [CIR] = 0.58, 95% CI: 0.41-0.78, p = 0.001) than intermittent supply areas. There was no significant association with hepatitis, cholera, or mortality of children <2 y old; however, our results were indicative of lower mortality of children <2 y old (CIR = 0.51, 95% CI: 0.22-1.07, p = 0.10) in continuous supply areas. The major limitations of our study were the potential for unmeasured confounding given the observational design and measurement bias from differential reporting of health symptoms given the nonblinded treatment. However, there was no significant difference in the prevalence of the negative control outcomes between study groups that would suggest undetected confounding or measurement bias. Continuous water supply had no significant overall association with diarrheal disease or ponderal growth in children <5 y old in Hubli-Dharwad; this might be due to point-of-use water contamination from continuing household storage and exposure to diarrheagenic pathogens through nonwaterborne routes. Continuous supply was associated with lower prevalence of dysentery in children in low-income households and lower typhoid fever incidence, suggesting that intermittently operated piped water systems are a significant transmission mechanism for Salmonella typhi and dysentery-causing pathogens in this urban population, despite centralized water treatment. Continuous supply was associated with reduced transmission, especially in the poorer higher-risk segments of the population.

R Factors in Strains of Salmonella typhi and Shigella dysenteriae 1 Isolated During Epidemics in Mexico: Classification by Compatibility

PubMed Central

Datta, Naomi; Olarte, J.

1974-01-01

All 17 Salmonella typhi strains tested from the epidemic in Mexico carried R factors of compatibility group H, conferring resistance to chloramphenicol, streptomycin, tetracycline, and sulfonamides. Some S. typhi strains carried, in addition, non-conjugative, ampicillin resistance plasmids and R factors of the I or A–C complex. All 20 Shigella dysenteriae 1 strains tested of epidemic origin carried O-group R factors. Ampicillin resistance in S. dysenteriae 1 was not proved to be plasmid borne. R factors of group H were not identified in any of the tested Mexican isolates other than S. typhi, but R factors of group O were identified in Escherichia coli, Shigella flexneri, and one strain of S. typhi, as well as in the epidemic S. dysenteriae. An R factor was identified which seemed to have two compatibility specificities, groups Iω and O. PMID:4599123

Revisiting typhoid fever surveillance in low and middle income countries: lessons from systematic literature review of population-based longitudinal studies.

PubMed

Mogasale, Vittal; Mogasale, Vijayalaxmi V; Ramani, Enusa; Lee, Jung Seok; Park, Ju Yeon; Lee, Kang Sung; Wierzba, Thomas F

2016-01-29

The control of typhoid fever being an important public health concern in low and middle income countries, improving typhoid surveillance will help in planning and implementing typhoid control activities such as deployment of new generation Vi conjugate typhoid vaccines. We conducted a systematic literature review of longitudinal population-based blood culture-confirmed typhoid fever studies from low and middle income countries published from 1(st) January 1990 to 31(st) December 2013. We quantitatively summarized typhoid fever incidence rates and qualitatively reviewed study methodology that could have influenced rate estimates. We used meta-analysis approach based on random effects model in summarizing the hospitalization rates. Twenty-two papers presented longitudinal population-based and blood culture-confirmed typhoid fever incidence estimates from 20 distinct sites in low and middle income countries. The reported incidence and hospitalizations rates were heterogeneous as well as the study methodology across the sites. We elucidated how the incidence rates were underestimated in published studies. We summarized six categories of under-estimation biases observed in these studies and presented potential solutions. Published longitudinal typhoid fever studies in low and middle income countries are geographically clustered and the methodology employed has a potential for underestimation. Future studies should account for these limitations.

The burden of typhoid fever in low- and middle-income countries: A meta-regression approach.

PubMed

Antillón, Marina; Warren, Joshua L; Crawford, Forrest W; Weinberger, Daniel M; Kürüm, Esra; Pak, Gi Deok; Marks, Florian; Pitzer, Virginia E

2017-02-01

Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs), so model-based estimates offer insights for decision-makers in the absence of readily available data. We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model. We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9-48.4 million). Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2-4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models. Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases.

Predicting the Impact of Vaccination on the Transmission Dynamics of Typhoid in South Asia: A Mathematical Modeling Study

PubMed Central

Pitzer, Virginia E.; Bowles, Cayley C.; Baker, Stephen; Kang, Gagandeep; Balaji, Veeraraghavan; Farrar, Jeremy J.; Grenfell, Bryan T.

2014-01-01

Background Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed. Methodology/Principal Findings We developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000–2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R 0) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 5–15 years following a one-time campaign. Conclusions/Significance We found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone. PMID:24416466

The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines.

PubMed

Thiem, Vu Dinh; Lin, Feng-Ying C; Canh, Do Gia; Son, Nguyen Hong; Anh, Dang Duc; Mao, Nguyen Duc; Chu, Chiayung; Hunt, Steven W; Robbins, John B; Schneerson, Rachel; Szu, Shousun C

2011-05-01

Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥ 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥ 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.

[Experimental study of the inoculative transmission of Rickettsia typhi by gamasid mites (Gamasidae) Ornithonyssus bacoti].

PubMed

Grabarev, P A; Suroviatkin, A V; Tikhonova, Iu Iu; Mishchenko, O A; Potapenko, O V

2009-01-01

The authors' studies have established that the concentration of Rickettsia typhi may increase about 100-fold in the infected Ornithonyssus bacoti mites. At the time, when on feeding 20 to 200 adult mites on guinea-pigs and albino rats 4 to 36 days after inoculation, they did not transmit Rickettsia typhi on blood sucking.

Lack of efflux mediated quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi A

PubMed Central

Baucheron, Sylvie; Monchaux, Isabelle; Le Hello, Simon; Weill, François-Xavier; Cloeckaert, Axel

2014-01-01

Salmonella enterica serovars Typhi and Paratyphi A isolates from human patients in France displaying different levels of resistance to quinolones or fluoroquinolones were studied for resistance mechanisms to these antimicrobial agents. All resistant isolates carried either single or multiple target gene mutations (i.e., in gyrA, gyrB, or parC) correlating with the resistance levels observed. Active efflux, through upregulation of multipartite efflux systems, has also been previously reported as contributing mechanism for other serovars. Therefore, we investigated also the occurrence of non-target gene mutations in regulatory regions affecting efflux pump expression. However, no mutation was detected in these regions in both Typhi and Paratyphi isolates of this study. Besides, no overexpression of the major efflux systems was observed for these isolates. Nevertheless, a large deletion of 2334 bp was identified in the acrS-acrE region of all S. Typhi strains but which did not affect the resistance phenotype. As being specific to S. Typhi, this deletion could be used for specific molecular detection purposes. In conclusion, the different levels of quinolone or FQ resistance in both S. Typhi and S. Paratyphi A seem to rely only on target modifications. PMID:24478769

Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha antagonist therapy.

PubMed

Peña-Sagredo, J L; Fariñas, M C; Perez-Zafrilla, B; Cruz-Valenciano, A; Crespo, M; Joven-Ibañez, B; Riera, E; Manero-Ruiz, F J; Chalmeta, I; Hernández, M V; Rodríguez-Gómez, M; Maíz, O; López, R; Cobo, T; Pita, J; Carmona, L; Gonzalez-Gay, M A

2009-01-01

The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies. The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain). Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection. Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.

Design of a Comprehensive Biochemistry and Molecular Biology Experiment: Phase Variation Caused by Recombinational Regulation of Bacterial Gene Expression

ERIC Educational Resources Information Center

Sheng, Xiumei; Xu, Shungao; Lu, Renyun; Isaac, Dadzie; Zhang, Xueyi; Zhang, Haifang; Wang, Huifang; Qiao, Zheng; Huang, Xinxiang

2014-01-01

Scientific experiments are indispensable parts of Biochemistry and Molecular Biology. In this study, a comprehensive Biochemistry and Molecular Biology experiment about "Salmonella enterica" serovar Typhi Flagellar phase variation has been designed. It consisted of three parts, namely, inducement of bacterial Flagellar phase variation,…

The burden of typhoid fever in low- and middle-income countries: A meta-regression approach

PubMed Central

Warren, Joshua L.; Crawford, Forrest W.; Weinberger, Daniel M.; Kürüm, Esra; Pak, Gi Deok; Marks, Florian; Pitzer, Virginia E.

2017-01-01

Background Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs), so model-based estimates offer insights for decision-makers in the absence of readily available data. Methods We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model. Results We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9–48.4 million). Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2–4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models. Conclusions Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases. PMID:28241011

Clinical and Haematological Manifestations of Typhoid Fever in Children in Eastern Turkey.

PubMed

Akbayram, S; Parlak, M; Dogan, M; Karasin, G; Akbayram, H T; Karaman, K

2016-01-12

Typhoid fever can involve various organs, leading to a wide range of presentations: from uncomplicated to complicated typhoid fever. The haematological changes are common in typhoid fever and include anaemia, leucopaenia, thrombocytopaenia and bleeding diathesis. This study was undertaken in order to determine the clinical and haematological presentation of typhoid fever in children. In this study, records of children and adolescents with typhoid fever aged under or equal to 16 years, admitted to Yuzuncu Yil University Hospital between 2010 and 2014, were analysed retrospectively. The cases (56%) were admitted to our hospital in July and October. Major symptoms of patients were abdominal pain (24%), arthralgia (21%) and fever (11%). In our study, decreased mean platelet volume (31%), eosinopaenia 20%), abnormal platelet count (19%), anaemia (16%), leucocytosis (16%) and eosinophilia (12%) were the most common haematological findings in the children. Typhoid fever is predominant in children at school age with a slight male predominance. Decreased mean platelet volume and abdominal pain might be useful as early diagnostic clues.

Role of T3SS-1 SipD Protein in Protecting Mice against Non-typhoidal Salmonella Typhimurium

PubMed Central

Jneid, Bakhos; Moreau, Karine; Plaisance, Marc; Rouaix, Audrey; Dano, Julie

2016-01-01

Background Salmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5 years and immunocompromised adults. Vaccines targeting typhoidal diseases are already marketed, but none protect against non-typhoidal Salmonella. The existence of multiple non-typhoidal Salmonella serotypes as well as emerging antibiotic resistance highlight the need for development of a broad-spectrum protective vaccine. All Salmonella spp. utilize two type III Secretion Systems (T3SS 1 and 2) to initiate infection, allow replication in phagocytic cells and induce systemic disease. T3SS-1, which is essential to invade epithelial cells and cross the barrier, forms an extracellular needle and syringe necessary to inject effector proteins into the host cell. PrgI and SipD form, respectively, the T3SS-1 needle and the tip complex at the top of the needle. Because they are common and highly conserved in all virulent Salmonella spp., they might be ideal candidate antigens for a subunit-based, broad-spectrum vaccine. Principal Findings We investigated the immunogenicity and protective efficacy of PrgI and SipD administered by subcutaneous, intranasal and oral routes, alone or combined, in a mouse model of Salmonella intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins, particularly SipD. Mice orally immunized with SipD alone or SipD combined with PrgI were protected against lethal intestinal challenge with Salmonella Typhimurium (100 Lethal Dose 50%) depending on antigen, route and adjuvant. Conclusions and Significance Salmonella T3SS SipD is a promising antigen for the development of a protective Salmonella vaccine, and could be developed for vaccination in tropical endemic areas to control infant mortality. PMID:27992422

Should close contacts of returning travellers with typhoid fever be protected by vaccination?

PubMed

Kantele, A

2015-03-17

Increasing international travel to areas endemic for typhoid fever correlates with increased risk for travellers to contract the disease. At home, the acutely ill/convalescent patients may pose some risk to their close contacts. In Finland an unofficial guideline suggests vaccination for close contacts of patients with acute typhoid fever; in other developed countries, routine typhoid vaccinations are only recommended to contacts of chronic carriers. This paper discusses the possibilities and limitations of prophylactic/post-exposure typhoid vaccination for contacts of patients with acute disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Novel Technique for Detecting Antibiotic-Resistant Typhoid from Rapid Diagnostic Tests

PubMed Central

Nic Fhogartaigh, Caoimhe; Dance, David A. B.; Davong, Viengmon; Tann, Pisey; Phetsouvanh, Rattanaphone; Turner, Paul; Newton, Paul N.

2015-01-01

Fluoroquinolone-resistant typhoid is increasing. An antigen-detecting rapid diagnotic test (RDT) can rapidly diagnose typhoid from blood cultures. A simple, inexpensive molecular technique performed with DNA from positive RDTs accurately identified gyrA mutations consistent with phenotypic susceptibility testing results. Field diagnosis combined with centralized molecular resistance testing could improve typhoid management and surveillance in low-resource settings. PMID:25762768

The agricultural antibiotic carbadox induces prophage and antibiotic resistance gene transfer in multidrug-resistant salmonella enterica serovar typhimurium DT104

USDA-ARS?s Scientific Manuscript database

Non-typhoidal Salmonella strains cause ~1 million cases of foodborne disease each year in the U.S. and are a leading cause of food-related deaths. The prevalence of multidrug-resistant (MDR) Salmonella serovars has increased over the last few decades, and infection with these strains has an increase...

Which cause of diffuse peritonitis is the deadliest in the tropics? A retrospective analysis of 305 cases from the South-West Region of Cameroon.

PubMed

Chichom-Mefire, Alain; Fon, Tabe Alain; Ngowe-Ngowe, Marcelin

2016-01-01

Acute diffuse peritonitis is a common surgical emergency worldwide and a major contributor to non-trauma related death toll. Its causes vary widely and are correlated with mortality. Community acquired peritonitis seems to play a major role and is frequently related to hollow viscus perforation. Data on the outcome of peritonitis in the tropics are scarce. The aim of this study is to analyze the impact of tropic latitude causes of diffuse peritonitis on morbidity and mortality. We retrospectively reviewed the records of 305 patients operated on for a diffuse peritonitis in two regional hospitals in the South-West Region of Cameroon over a 7 years period. The contributions of various causes of peritonitis to morbidity and mortality were analyzed. The diagnosis of diffuse peritonitis was suggested on clinical ground only in more than 93 % of cases. The most common causes of diffuse peritonitis included peptic ulcer perforation (n = 69), complications of acute appendicitis (n = 53) and spontaneous perforations of the terminal ileum (n = 43). A total of 142 complications were recorded in 96 patients (31.5 % complication rate). The most common complications included wound dehiscence, sepsis, prolonged paralytic ileus and multi-organ failure. Patients with typhoid perforation of the terminal ileum carried a significantly higher risk of developing a complication (p = 0.002). The overall mortality rate was 15.1 %. The most common cause of death was septic shock. Differential analysis of mortality of various causes of peritonitis indicated that the highest contributors to death toll were typhoid perforation of terminal ileum (34.7 % of deaths), post-operative peritonitis (19.5 %) and peptic ulcer perforation (15.2 %). The diagnosis of diffuse peritonitis can still rely on clinical assessment alone in the absence of sophisticated imaging tools. Peptic ulcer and typhoid perforations are still major contributors to death toll. Patients presenting with these conditions require specific attention and prevention policies must be reinforced.

Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi.

PubMed

Chao, Chien-Chung; Belinskaya, Tatyana; Zhang, Zhiwen; Ching, Wei-Mei

2015-01-01

Sensitive, specific and rapid diagnostic tests for the detection of Orientia tsutsugamushi (O. tsutsugamushi) and Rickettsia typhi (R. typhi), the causative agents of scrub typhus and murine typhus, respectively, are necessary to accurately and promptly diagnose patients and ensure that they receive proper treatment. Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. tsutsugamushi or 17 kDa gene of R. typhi. The RPA assay was capable of detecting O. tsutsugamushi or R. typhi at levels comparable to that of the quantitative PCR method. Both the RPA-nfo and RPA-exo methods performed similarly with regards to sensitivity when detecting the 17 kDa gene of R. typhi. On the contrary, RPA-exo performed better than RPA-nfo in detecting the 47 kDa gene of O. tsutsugamushi. The clinical performance of the O. tsutsugamushi RPA assay was evaluated using either human patient samples or infected mouse samples. Eight out of ten PCR confirmed positives were determined positive by RPA, and all PCR confirmed negative samples were negative by RPA. Similar results were obtained for R. typhi spiked patient sera. The assays were able to differentiate O. tsutsugamushi and R. typhi from other phylogenetically related bacteria as well as mouse and human DNA. Furthermore, the RPA-nfo reaction was completed in 20 minutes at 37°C followed by a 10 minute incubation at room temperature for development of an immunochromatographic strip. The RPA-exo reaction was completed in 20 minutes at 39°C. The implementation of a cross contamination proof cassette to detect the RPA-nfo fluorescent amplicons provided an alternative to regular lateral flow detection strips, which are more prone to cross contamination. The RPA assays provide a highly time-efficient, sensitive and specific alternative to other methods for diagnosing scrub typhus or murine typhus.

Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi

PubMed Central

Chao, Chien-Chung; Belinskaya, Tatyana; Zhang, Zhiwen; Ching, Wei-Mei

2015-01-01

Sensitive, specific and rapid diagnostic tests for the detection of Orientia tsutsugamushi (O. tsutsugamushi) and Rickettsia typhi (R. typhi), the causative agents of scrub typhus and murine typhus, respectively, are necessary to accurately and promptly diagnose patients and ensure that they receive proper treatment. Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. tsutsugamushi or 17 kDa gene of R. typhi. The RPA assay was capable of detecting O. tsutsugamushi or R. typhi at levels comparable to that of the quantitative PCR method. Both the RPA-nfo and RPA-exo methods performed similarly with regards to sensitivity when detecting the 17 kDa gene of R. typhi. On the contrary, RPA-exo performed better than RPA-nfo in detecting the 47 kDa gene of O. tsutsugamushi. The clinical performance of the O. tsutsugamushi RPA assay was evaluated using either human patient samples or infected mouse samples. Eight out of ten PCR confirmed positives were determined positive by RPA, and all PCR confirmed negative samples were negative by RPA. Similar results were obtained for R. typhi spiked patient sera. The assays were able to differentiate O. tsutsugamushi and R. typhi from other phylogenetically related bacteria as well as mouse and human DNA. Furthermore, the RPA-nfo reaction was completed in 20 minutes at 37oC followed by a 10 minute incubation at room temperature for development of an immunochromatographic strip. The RPA-exo reaction was completed in 20 minutes at 39oC. The implementation of a cross contamination proof cassette to detect the RPA-nfo fluorescent amplicons provided an alternative to regular lateral flow detection strips, which are more prone to cross contamination. The RPA assays provide a highly time-efficient, sensitive and specific alternative to other methods for diagnosing scrub typhus or murine typhus. PMID:26161793

Typhoid fever vaccination strategies.

PubMed

Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

2015-06-19

Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by Elsevier Ltd.

[Family practice in a rural environment in the west of France (1908-1920): chronicle of mortality].

PubMed

Hidier, Jacques

2009-01-01

This paper reports about a manuscript from Doctor Pelletier who accounted the causes of death rate in a village of the Vendée: pneumopathy, typhoid, diarrhoea linked to unhealthiness provoked by stagnant waters.

A Perspective on Invasive Salmonella Disease in Africa.

PubMed

Crump, John A; Heyderman, Robert S

2015-11-01

Salmonella enterica is a leading cause of community-acquired bloodstream infection in Africa. The contribution of typhoidal and nontyphoidal Salmonella serovars to invasive disease varies considerably in place and time, even within the same country. Nonetheless, many African countries are now thought to experience typhoid fever incidence >100 per 100,000 per year with approximately 1% of patients dying. Invasive nontyphoidal Salmonella (iNTS) disease was estimated to cause 3.4 million illnesses and 681 316 deaths in 2010, with the most disease in Africa. Antimicrobial drug resistance is a growing problem in S. enterica that threatens to further compromise patient outcomes. Reservoirs for nontyphoidal Salmonella and the predominant routes of transmission for typhoidal and nontyphoidal Salmonella are not well understood in Africa, hampering the design of evidence-based, non-vaccine- and vaccine-based prevention measures. It is difficult to distinguish clinically invasive Salmonella disease from febrile illnesses caused by other pathogens. Blood cultures are the mainstay of laboratory diagnosis, but lack sensitivity due to the low magnitude of bacteremia, do not produce results at point of care, and are not widely available in Africa. Serologic approaches to diagnosis remain inaccurate, and nucleic acid amplification tests are also compromised by low concentrations of bacteria. High-throughput whole-genome sequencing, together with a range of novel analytic pipelines, has provided new insights into the complex pattern of epidemiology, pathogenesis, and host adaptation. Concerted efforts are therefore needed to apply these new tools in the context of high-quality field surveillance to improve diagnosis, patient management, control, and prevention of invasive Salmonella infections in Africa. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Review of current typhoid fever vaccines, cross-protection against paratyphoid fever, and the European guidelines.

PubMed

Zuckerman, Jane N; Hatz, Christoph; Kantele, Anu

2017-10-01

Typhoid and paratyphoid fever remain a global health problem, which - in non-endemic countries - are mainly seen in travelers, particularly in VFRs (visiting friends and relatives), with occasional local outbreaks occurring. A rise in anti-microbial resistance emphasizes the role of preventive measures, especially vaccinations against typhoid and paratyphoid fever for travelers visiting endemic countries. Areas covered: This state-of-the-art review recapitulates the epidemiology and mechanisms of disease of typhoid and paratyphoid fever, depicts the perspective of non-endemic countries and travelers (VFRs), and collectively presents current European recommendations for typhoid fever vaccination. We provide a brief overview of available (and developmental) vaccines in Europe, present current data on cross-protection to S. Paratyphi, and aim to provide a background for typhoid vaccine decision-making in travelers. Expert commentary: European recommendations are not harmonized. Experts must assess vaccination of travelers based on current country-specific recommendations. Travel health practitioners should be aware of the issues surrounding vaccination of travelers and be motivated to increase awareness of typhoid and paratyphoid fever risks.

Risk factors associated with typhoid fever in children aged 2-16 years in Karachi, Pakistan.

PubMed

Khan, M I; Ochiai, R L; Soofi, S B; Von-Seidlein, L; Khan, M J; Sahito, S M; Habib, M A; Puri, M K; Park, J K; You, Y A; Ali, M; Nizami, S Q; Acosta, C J; Bradley-Sack, R; Clemens, J D; Bhutta, Z A

2012-04-01

We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household- and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0·89, 95% confidence interval (CI) 0·83-0·95], was higher with an increase in population density (RR 1·13, 95% CI 1·05-1·21) and was lower in the households using a safe drinking-water source (RR 0·63, 95% CI 0·41-0·99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan.

Typhoid fever in paediatric patients in Quetta, Balochistan, Pakistan.

PubMed

Naeem Khan, Muhammad; Shafee, Muhammad; Hussain, Kamran; Samad, Abdul; Arif Awan, Muhammad; Manan, Abdul; Wadood, Abdul

2013-07-01

To determine the seropositivity of typhoid fever in febrile pediatric patients presenting to tertiary care center. This observational study was conducted at Children Hospital Quetta (CHQ) from July 2011 to March 2012. The children with three or more days fever, no obvious focus of infection and clinically suspected of typhoid fever were screened. Sterile Blood samples were obtained from febrile patients and Widal and Typhidot® tests were performed for the diagnosis of Typhoid fever in the suspected populations. Total of 2964 clinically suspected patients were screened for typhoid fever. Of these, 550 (18.6%) patients were positive serologically. The higher prevalence of the disease in hot summer season and increasing pattern of the disease was observed in summer days. The disease was higher in school age children under 5-10 years. Although non-significant association was observed on sex basis. The findings highlight the considerable burden of typhoid fever in pre-school and school-aged children. The variation in the disease pattern has also been observed under seasonal variation and different age groups, all of which need to be considered in deliberations to control the typhoid fever.

Prevalence of antimicrobial resistance in Salmonella serotype Hadar isolated from humans, retail meat, and food animals at slaughter, United States, NARMS 1996-2008

USDA-ARS?s Scientific Manuscript database

Background Non-Typhi Salmonella (NTS) is a leading cause of bacterial gastroenteritis in the United States. Although most infections are self-limited, antibiotic treatment is essential for severe illness. Use of antimicrobial agents in food animals contributes to resistance in NTS. Multidrug resis...

Reports of Military Observers Attached to the Armies in Manchuria during the Russo-Japanese War. Part 2

DTIC Science & Technology

1906-10-01

pressure, almost petechial in character, as if there was a slight admixture of typhus infection. Such cases were always serious. Typhoid fever is not rare...of typhoid fever , 15 of typhus, and 9 of recurrent fever . The number of typhoid- fever cases, how- ever, rapidly increased up to 951 on August 26...east of Lake Baikal (about 570,000 men), was as follows: Dysentery....................... ............... Typhoid fever

Role of computed tomography of abdomen in difficult to diagnose typhoid fever: a case series.

PubMed

Hafeez, Wajid; Rajalakshmi, S; Sripriya, S; Madhu Bashini, M

2018-04-01

Background and Aim Diagnosis of typhoid is challenging when blood cultures fail to isolate Salmonella species. We report our experience with interpreting computed tomography (CT) abdomen findings in a case series of typhoid fever. Methods The case series consisted of patients who had a CT abdomen done as part of their investigations and a final diagnosis of typhoid fever. The CT films were reviewed and findings evaluated for distinctive features. Results During 2011-2017, 11 patients met the inclusion criteria. Indication for CT was pyrexia of unknown origin in the majority of patients. Review of CT films revealed mesenteric lymphadenopathy (100%), terminal ileum thickening (85%), hepatosplenomegaly (45%), retroperitoneal lymphadenopathy (18%) and ascites (9%). Conclusions Enhancing discrete mesenteric lymphadenopathy and terminal ileum thickening are non-specific findings noted in typhoid fever. Absence of matted necrotic nodes and peritoneal thickening rule out tuberculosis and raise suspicion of typhoid fever in endemic regions.

Significance and value of the Widal test in the diagnosis of typhoid fever in an endemic area.

PubMed Central

Pang, T; Puthucheary, S D

1983-01-01

The diagnostic value of the Widal test was assessed in an endemic area. The test was done on 300 normal individuals, 297 non-typhoidal fevers and 275 bacteriologically proven cases of typhoid. Of 300 normal individuals, 2% had an H agglutinin titre of 1/160 and 5% had an O agglutinin titre of 1/160. On the basis of these criteria a significant H and/or O agglutinin titre of 1/320 or more was observed in 93-97% of typhoid cases and in only 3% of patients with non-typhoidal fever. Of the sera from typhoid cases which gave a significant Widal reaction, the majority (79.9%) showed increases in both H and O agglutinins and 51 of 234 (21.8%) of these sera were collected in the first week of illness. The significance and implications of these findings are discussed. PMID:6833514

Salmonella interactions with plants and their associated microbiota

USDA-ARS?s Scientific Manuscript database

The increase in the incidence of gastroenteritis outbreaks linked to the consumption of foods of plant origin has ignited public concern and scientific interest in understanding interactions of human enteric pathogens with plants. Enteric disease caused by non-typhoidal Salmonella is a major public ...

Phase I clinical trial of O-Acetylated pectin conjugate, a plant polysaccharide based typhoid vaccine

PubMed Central

Szu, Shousun C.; Lin, Kimi F-Y; Hunt, Steven; Chu, Chiayung; Thinh, Nguyen Duc

2014-01-01

Background Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial. Methods Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18–45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed. Results No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4 fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R2 = 0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults. Conclusion The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. PMID:24657719

Typhoid Fever surveillance and vaccine use - South-East Asia and Western Pacific regions, 2009-2013.

PubMed

Date, Kashmira A; Bentsi-Enchill, Adwoa D; Fox, Kimberley K; Abeysinghe, Nihal; Mintz, Eric D; Khan, M Imran; Sahastrabuddhe, Sushant; Hyde, Terri B

2014-10-03

Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia. Safe water, adequate sanitation, appropriate personal and food hygiene, and vaccination are the most effective strategies for prevention and control. In 2008, the World Health Organization (WHO) recommended use of available typhoid vaccines to control endemic disease and outbreaks and strengthening of typhoid surveillance to improve disease estimates and identify high-risk populations (e.g., persons without access to potable water and adequate sanitation). This report summarizes the status of typhoid surveillance and vaccination programs in the WHO South-East Asia (SEAR) and Western Pacific regions (WPR) during 2009-2013, after the revised WHO recommendations. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form on Immunization, a supplemental survey of surveillance and immunization program managers, and published literature. During 2009-2013, 23 (48%) of 48 countries and areas of SEAR (11) and WPR (37) collected surveillance or notifiable disease data on typhoid cases, with most surveillance activities established before 2008. Nine (19%) countries reported implementation of typhoid vaccination programs or recommended vaccine use during 2009-2013. Despite the high incidence, typhoid surveillance is weak in these two regions, and vaccination efforts have been limited. Further progress toward typhoid fever prevention and control in SEAR and WPR will require country commitment and international support for enhanced surveillance, targeted use of existing vaccines and availability of newer vaccines integrated within routine immunization programs, and integration of vaccination with safe water, sanitation, and hygiene measures.

Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.

PubMed

Uneke, C J

2008-06-01

Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987-2007), to highlight the diagnostic challenges and the public health implications. Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

Nalidixic Acid-Resistant Salmonella enterica Serotype Typhi Presenting as a Primary Psoas Abscess: Case Report and Review of the Literature

PubMed Central

Shakespeare, William A.; Davie, Daniel; Tonnerre, Claude; Rubin, Michael A.; Strong, Michael; Petti, Cathy A.

2005-01-01

We report an unusual case of Salmonella enterica serotype Typhi presenting as a primary psoas abscess. The isolate tested susceptible to ciprofloxacin but resistant to nalidixic acid in vitro, a pattern associated with fluoroquinolone therapeutic failures. We review the literature for serovar Typhi psoas abscess in the absence of bacteremia and discuss the importance of identifying isolates with reduced susceptibility to fluoroquinolones. PMID:15695728

Decontamination of Bioaerosols within Engineering Tolerances of Aircraft Materials

DTIC Science & Technology

2012-09-04

sources with intestinal typhoid bacteria. They also released plague infected fleas over several villages in China and Mongolia in 1941. Around the...smallpox, Marburg, Ebola, and Q fever . During their program, the Soviets produced more than 100 tons of anthrax, 20 tons of plague, and 20 tons of...Filoviridae, Bunyaviridae, and Flavividae families, which cause hemorrhagic fevers . The category B viruses include several arboviruses, which cause

Guillain-Barré syndrome associated with typhoid fever. A case study in the Fiji Islands.

PubMed

May, William; Senitiri, Iokimi

2010-09-01

Guillian-Barré Syndome is a very rare neurological complication of typhoid. We report a young girl with blood culture proven typhoid septicaemia that developed this very rare neurological complication of the disease. Following treatment with intravenous antibiotics she improved but developed the complications during the third week of her illness while admitted in hospital. To our knowledge this neurological complication of typhoid has never been reported in Fiji.

Typhoid fever in a Tertiary Hospital in Nigeria: Another look at the Widal agglutination test as a preferred option for diagnosis.

PubMed

Enabulele, Osahon; Awunor, Simeon Nyemike

2016-01-01

Single Widal agglutination test rather than blood culture, is commonly employed to diagnose typhoid fever in Nigeria. We took another look at the Widal agglutination test as a preferred option for diagnosis of typhoid fever by determining the specificity and sensitivity of Widal agglutination test in febrile adult patients. Two hundred and seventy-one blood samples from consecutive adults (>18 years) with febrile illness attending the General Practice Clinic of the University of Benin Teaching Hospital were tested using the Widal agglutination test, blood culture, and malaria parasite test on each sample to establish the diagnosis of typhoid fever. Of the 271 blood samples 124 (45.76%) were positive following a Widal agglutination test, 60 (22.10%) blood samples grew Salmonella organisms on blood culture while 55 (20.29%) blood samples showed a co-infection of typhoid fever and malaria. A sensitivity of 35%, specificity of 51%, positive predictive value of 17%, and a negative predictive value of 73% were observed for Widal agglutination test as a diagnostic modality for typhoid fever infection. A single Widal agglutination test is not a valid diagnostic option for typhoid fever while co-infection with malaria parasite is the preponderant microbiological finding in typhoid fever infections. The severity of malaria parasitemia is associated with positive titers on Widal test.

Typhoid fever in a Tertiary Hospital in Nigeria: Another look at the Widal agglutination test as a preferred option for diagnosis

PubMed Central

Enabulele, Osahon; Awunor, Simeon Nyemike

2016-01-01

Background: Single Widal agglutination test rather than blood culture, is commonly employed to diagnose typhoid fever in Nigeria. We took another look at the Widal agglutination test as a preferred option for diagnosis of typhoid fever by determining the specificity and sensitivity of Widal agglutination test in febrile adult patients. Materials and Methods: Two hundred and seventy-one blood samples from consecutive adults (>18 years) with febrile illness attending the General Practice Clinic of the University of Benin Teaching Hospital were tested using the Widal agglutination test, blood culture, and malaria parasite test on each sample to establish the diagnosis of typhoid fever. Results: Of the 271 blood samples 124 (45.76%) were positive following a Widal agglutination test, 60 (22.10%) blood samples grew Salmonella organisms on blood culture while 55 (20.29%) blood samples showed a co-infection of typhoid fever and malaria. A sensitivity of 35%, specificity of 51%, positive predictive value of 17%, and a negative predictive value of 73% were observed for Widal agglutination test as a diagnostic modality for typhoid fever infection. Conclusion: A single Widal agglutination test is not a valid diagnostic option for typhoid fever while co-infection with malaria parasite is the preponderant microbiological finding in typhoid fever infections. The severity of malaria parasitemia is associated with positive titers on Widal test. PMID:27397952

Clinical and epidemiological features of typhoid fever in Pemba, Zanzibar: assessment of the performance of the WHO case definitions.

PubMed

Thriemer, Kamala; Ley, Benedikt; Ley, Benedikt B; Ame, Shaali S; Deen, Jaqueline L; Pak, Gi Deok; Chang, Na Yoon; Hashim, Ramadhan; Schmied, Wolfgang Hellmut; Busch, Clara Jana-Lui; Nixon, Shanette; Morrissey, Anne; Puri, Mahesh K; Ochiai, R Leon; Wierzba, Thomas; Clemens, John D; Ali, Mohammad; Jiddawi, Mohammad S; von Seidlein, Lorenz; Ali, Said M

2012-01-01

The gold standard for diagnosis of typhoid fever is blood culture (BC). Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever. Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1:80. Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.

Typhoid vaccination for international travelers from Greece visiting developing countries.

PubMed

Smeti, Paraskevi; Pavli, Androula; Katerelos, Panagiotis; Maltezou, Helena C

2014-01-01

Typhoid fever is one of the most common diagnoses in returned international travelers. Our aim was to study the typhoid vaccine prescription practices for travelers from Greece visiting developing countries. A prospective questionnaire-based study was conducted during 2009-2012 in 57 Public Health Departments, which are the only sources of typhoid vaccine in Greece. A total of 3,680 travelers were studied (median age: 38.1 years). Typhoid vaccine was delivered to 1,108 (30.1%) of them. Of those who traveled to sub-Saharan Africa, South America, the Middle East, the Indian subcontinent, Southeast Asia, South Africa, East Asia, North Africa, and Central America, 31.6, 17.1, 35, 44.2, 36.9, 31, 17.7, 31.6, and 36.8% received typhoid vaccine, respectively. Of travelers who stayed <1 month, 1 to <3 months, 3 to <6 months, and ≥6 months, 21.4, 63.1, 32.3, and 34.9% were vaccinated, respectively. According to the purpose of travel, typhoid vaccine was administered to 32.7% of those who traveled for leisure, to 28.8% of those who traveled for business, and to 24.1% of those visiting friends and relatives (VFRs). Of travelers who stayed in urban areas, rural areas, and urban and rural areas, 36.3, 30.1, and 26.8% were vaccinated, respectively. The majority of travelers who received the typhoid vaccine stayed in camps (62.9%) or at local residences (41%). Typhoid vaccine administration was statistically significantly associated with destination, duration of travel, purpose of travel, area of stay, and type of accommodation. There is a need to increase awareness of travelers and public health professionals for typhoid vaccination and particularly for high-risk groups of travelers, such as travelers to the Indian subcontinent and VFRs. Strategies for continuing professional education should be developed for travel health professionals. © 2013 International Society of Travel Medicine.

A cost-effectiveness analysis of typhoid fever vaccines in US military personnel.

PubMed

Warren, T A; Finder, S F; Brier, K L; Ries, A J; Weber, M P; Miller, M R; Potyk, R P; Reeves, C S; Moran, E L; Tornow, J J

1996-11-01

Typhoid fever has been a problem for military personnel throughout history. A cost-effectiveness analysis of typhoid fever vaccines from the perspective of the US military was performed. Currently 3 vaccine preparations are available in the US: an oral live Type 21A whole cell vaccine; a single-dose parenteral, cell subunit vaccine; and a 2-dose parenteral heat-phenol killed, whole cell vaccine. This analysis assumed all vaccinees were US military personnel. Two pharmacoeconomic models were developed, one for personnel who have not yet been deployed, and the other for personnel who are deployed to an area endemic for typhoid fever. Drug acquisition, administration, adverse effect and lost work costs, as well as the costs associated with typhoid fever, were included in this analysis. Unique military issues, typhoid fever attack rates, vaccine efficacy, and compliance with each vaccine's dosage regimen were included in this analysis. A sensitivity analysis was performed to test the robustness of the models. Typhoid fever immunisation is not cost-effective for US military personnel unless they are considered imminently deployable or are deployed. The most cost-effective vaccine for US military personnel is the single-dose, cell subunit parenteral vaccine.

Typhoid fever in paediatric patients in Quetta, Balochistan, Pakistan

PubMed Central

Naeem Khan, Muhammad; Shafee, Muhammad; Hussain, Kamran; Samad, Abdul; Arif Awan, Muhammad; Manan, Abdul; Wadood, Abdul

2013-01-01

Objectives: To determine the seropositivity of typhoid fever in febrile pediatric patients presenting to tertiary care center. Methods: This observational study was conducted at Children Hospital Quetta (CHQ) from July 2011 to March 2012. The children with three or more days fever, no obvious focus of infection and clinically suspected of typhoid fever were screened. Sterile Blood samples were obtained from febrile patients and Widal and Typhidot® tests were performed for the diagnosis of Typhoid fever in the suspected populations. Results: Total of 2964 clinically suspected patients were screened for typhoid fever. Of these, 550 (18.6%) patients were positive serologically. The higher prevalence of the disease in hot summer season and increasing pattern of the disease was observed in summer days. The disease was higher in school age children under 5-10 years. Although non-significant association was observed on sex basis. Conclusion: The findings highlight the considerable burden of typhoid fever in pre-school and school-aged children. The variation in the disease pattern has also been observed under seasonal variation and different age groups, all of which need to be considered in deliberations to control the typhoid fever. PMID:24353661

Evaluation of Proposed Dredged Material Disposal Alternatives for New York/New Jersey Harbor. Phase 1

DTIC Science & Technology

1988-08-01

following initial incubation of the inoculum in lactose broth. The presence of Vibrio parahemolyticus was determined using trypticase citrate 0 bile salts...SaZmonella (enteritis), SalmonelZa typhosa (typhoid fever), ShigeZla (dysentery), and Vibrio cholerae (cholera). The organisms causing these diseases do not

A comparison of non-typhoidal Salmonella from humans and food animals using pulsed-field gel electrophoresis and antimicrobial susceptibility patterns

USDA-ARS?s Scientific Manuscript database

Salmonellosis is one of the most important foodborne diseases affecting humans. To characterize the relationship between Salmonella causing human infections and their food animal reservoirs, we compared pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility patterns of non-typhoida...

SALMONELLA ENTERICA SEROVAR ENTERITIDIS INFECTION MODULATES DIVERSE FUNCTIONAL PROCESSES OF CHICKEN MACROPHAGE AT THE TRANSCRIPTIONAL LEVEL

USDA-ARS?s Scientific Manuscript database

Salmonella enterica serovar Enteritidis (SE) is a major etiologic agent of non-typhoid salmonellosis. The organisms colonize adult chicken hosts without causing overt clinical signs. The immunological mechanisms underlying the silent and persistent infection of chickens by SE are not clearly underst...

Isolation of QseC-regulated genes in Salmonella enterica serovar Typhimurium by transposon mutgagenesis

USDA-ARS?s Scientific Manuscript database

Non-typhoidal Salmonella, a leading cause of U.S. foodborne disease and food-related deaths, often asymptomatically colonizes food-producing animals. In fact, >50% of U.S. swine production facilities test positive for Salmonella. The multidrug-resistant (MDR) Salmonella Typhimurium DT104 NCTC13348 c...

Gold nanoparticles as efficient antimicrobial agents for Escherichia coli and Salmonella typhi

PubMed Central

2013-01-01

Background It is imperative to eliminate bacteria present in water in order to avoid problems in healthy. Escherichia coli and Salmonella typhi bacteria are two common pollutants and they are developing resistance to some of the most used bactericide. Therefore new biocide materials are being tested. Thus, gold nanoparticles are proposed to inhibit the growth of these two microorganisms. Results Gold nanoparticles were supported onto clinoptilolite, mordenite and faujasite zeolites. Content of gold in materials varied between 2.3 and 2.8 wt%. The size, dispersion and roughness of gold nanoparticles were highly dependent of the zeolite support. The faujasite support was the support where the 5 nm nanoparticles were highly dispersed. The efficiency of gold-zeolites as bactericides of Escherichia coli and Salmonella typhi was determined by the zeolite support. Conclusions Gold nanoparticles dispersed on zeolites eliminate Escherichia coli and Salmonella typhi at short times. The biocidal properties of gold nanoparticles are influenced by the type of support which, indeed, drives key parameters as the size and roughness of nanoparticles. The more actives materials were pointed out Au-faujasite. These materials contained particles sized 5 nm at surface and eliminate 90–95% of Escherichia coli and Salmonella typhi colonies. PMID:23331621

9 CFR 147.5 - The microagglutination test for pullorum-typhoid.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false The microagglutination test for pullorum-typhoid. 147.5 Section 147.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... IMPROVEMENT PLAN Blood Testing Procedures § 147.5 The microagglutination test for pullorum-typhoid. Routinely...

9 CFR 147.5 - The microagglutination test for pullorum-typhoid.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false The microagglutination test for pullorum-typhoid. 147.5 Section 147.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... IMPROVEMENT PLAN Blood Testing Procedures § 147.5 The microagglutination test for pullorum-typhoid. Routinely...

9 CFR 147.5 - The microagglutination test for pullorum-typhoid.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false The microagglutination test for pullorum-typhoid. 147.5 Section 147.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... IMPROVEMENT PLAN Blood Testing Procedures § 147.5 The microagglutination test for pullorum-typhoid. Routinely...

9 CFR 147.5 - The microagglutination test for pullorum-typhoid.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false The microagglutination test for pullorum-typhoid. 147.5 Section 147.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... IMPROVEMENT PLAN Blood Testing Procedures § 147.5 The microagglutination test for pullorum-typhoid. Routinely...

9 CFR 147.5 - The microagglutination test for pullorum-typhoid.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false The microagglutination test for pullorum-typhoid. 147.5 Section 147.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... IMPROVEMENT PLAN Blood Testing Procedures § 147.5 The microagglutination test for pullorum-typhoid. Routinely...

Immunogenicity of One Dose of Vero Cell Culture-Derived Japanese Encephalitis (JE) Vaccine in Adults Previously Vaccinated with Mouse Brain-Derived JE Vaccine

DTIC Science & Technology

2012-03-06

redness, pain, and swelling) and five systemic symp- toms ( fever , headache, rash, vomiting or diarrhea, and muscle aches) on each of the 4 days following...counts between the two cohorts defined by previous JE vaccine status. b Other vaccines received included influenza (n = 5 subjects), typhoid (n = 2...subjects), typhoid (n = 3), hepatitis A, hepatitis B, and typhoid (n = 2), anthrax and typhoid (n = 1), and hepatitis A and hepatitis B (n = 1). d For dose

Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam.

PubMed

Dunstan, S J; Stephens, H A; Blackwell, J M; Duc, C M; Lanh, M N; Dudbridge, F; Phuong, C X; Luxemburger, C; Wain, J; Ho, V A; Hien, T T; Farrar, J; Dougan, G

2001-01-15

The influence of genes of the major histocompatibility complex (MHC) class II and class III loci on typhoid fever susceptibility was investigated. Individuals with blood culture-confirmed typhoid fever and control subjects from 2 distinct geographic locations in southern Vietnam were genotyped for HLA-DRB1 and HLA-DQB1 alleles, the gene that encodes tumor necrosis factor (TNF)-alpha (TNFA [-238] and TNFA [-308]), the gene that encodes lymphotoxin-alpha, and alleles of the TNF-alpha microsatellite. HLA-DRB1*0301/6/8, HLA-DQB1*0201-3, and TNFA*2 (-308) were associated with susceptibility to typhoid fever, whereas HLA-DRB1*04, HLA-DQB1*0401/2, and TNFA*1 (-308) were associated with disease resistance. The frequency of all possible haplotypes of the 3 individually associated loci were estimated and were found to be significantly different in typhoid case patients and control subjects (chi2=55.56, 32 df; P=.006). Haplotypes that were either protective (TNFA*1 [-308].DRB1*04) or predisposed individuals to typhoid fever (TNFA*2 [-308].DRB1*0301) were determined. This report identifies a genetic association in humans between typhoid fever and MHC class II and III genes.

Clinically and Microbiologically Derived Azithromycin Susceptibility Breakpoints for Salmonella enterica Serovars Typhi and Paratyphi A

PubMed Central

Thieu, Nga Tran Vu; Dolecek, Christiane; Karkey, Abhilasha; Gupta, Ruchi; Turner, Paul; Dance, David; Maude, Rapeephan R.; Ha, Vinh; Tran, Chinh Nguyen; Thi, Phuong Le; Be, Bay Pham Van; Phi, La Tran Thi; Ngoc, Rang Nguyen; Ghose, Aniruddha; Dongol, Sabina; Campbell, James I.; Thanh, Duy Pham; Thanh, Tuyen Ha; Moore, Catrin E.; Sona, Soeng; Gaind, Rajni; Deb, Monorama; Anh, Ho Van; Van, Sach Nguyen; Tinh, Hien Tran; Day, Nicholas P. J.; Dondorp, Arjen; Thwaites, Guy; Faiz, Mohamed Abul; Phetsouvanh, Rattanaphone; Newton, Paul; Basnyat, Buddha; Farrar, Jeremy J.; Baker, Stephen

2015-01-01

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤16 μg/ml or disk inhibition zone size of ≥13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A. PMID:25733500

9 CFR 145.83 - Terminology and classification; flocks and products.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-typhoid control under official supervision; (B) All hatchery supply flocks within the State are qualified as U.S. Pullorum-Typhoid Clean or have met equivalent requirements for pullorum-typhoid control under... laboratory and any group D Salmonella samples have been serotyped: (A) A 25-gram sample of meconium from the...

9 CFR 145.83 - Terminology and classification; flocks and products.

Code of Federal Regulations, 2011 CFR

2011-01-01

...-typhoid control under official supervision; (B) All hatchery supply flocks within the State are qualified as U.S. Pullorum-Typhoid Clean or have met equivalent requirements for pullorum-typhoid control under... laboratory and any group D Salmonella samples have been serotyped: (A) A 25-gram sample of meconium from the...

9 CFR 145.83 - Terminology and classification; flocks and products.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-typhoid control under official supervision; (B) All hatchery supply flocks within the State are qualified as U.S. Pullorum-Typhoid Clean or have met equivalent requirements for pullorum-typhoid control under... laboratory and any group D Salmonella samples have been serotyped: (A) A 25-gram sample of meconium from the...

Unusual complication of toxic megacolon in typhoid colitis.

PubMed

Arun Babu, Thirunavukkarasu; Ananthakrishnan, Shanthi; Jayakumar, P; Kullu, Poonam

2014-05-01

Colitis is a rare manifestation of enteric fever in children. Toxic megacolon complicating typhoid colitis is even rarer and requires early recognition and aggressive management due to the high mortality associated with this condition. The authors report a rare case of Toxic megacolon secondary to typhoid colitis in a seven-year-old girl.

Association between Helicobacter pylori infection and increased risk of typhoid fever.

PubMed

Bhan, Maharaj K; Bahl, Rajiv; Sazawal, Sunil; Sinha, Anju; Kumar, Ramesh; Mahalanabis, Dilip; Clemens, John D

2002-12-15

Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.

What Ails Public Health?

ERIC Educational Resources Information Center

Alcabes, Philip

2007-01-01

Public health, once the gem of American social programs, has turned to dross. During the 20th century, the public-health sector wiped smallpox and polio off the U.S. map; virtually eliminated rickets, rubella, and goiter; stopped epidemic typhoid and yellow fever; and brought tuberculosis--once the leading cause of death in U.S. cities--under…

The relationship between the immune response and susceptibility to Salmonella enterica serovar Enteritidis infection in the laying hen

USDA-ARS?s Scientific Manuscript database

Chicken eggs are one of the main sources of human salmonellosis, with Salmonella enterica serovar Enteritidis the most frequent cause of human non-typhoid salmonellosis. Laying hens colonized with S. Enteritidis generally do not show clinical signs. The bacteria colonize and invade the intestinal ...

Diffuse abdominal gallium-67 citrate uptake in salmonella infections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garty, I.; Koren, A.

1987-11-01

Two pediatric patients with salmonella infections (one with typhoid fever and the second with salmonella C2 gastroenteritis), had a diffuse abdominal uptake of Ga-67 citrate. The possible explanation for this finding is discussed. Salmonella infection should be included as a cause in the differential diagnosis of diffuse accumulation of Ga-67 citrate.

The agricultural antibiotic carbadox induces generalized transducing phage in multidrug-resistant Salmonella enterica serovar Typhimurium DT104

USDA-ARS?s Scientific Manuscript database

Non-typhoidal Salmonella, a leading cause of U.S. foodborne disease and food-related deaths, often asymptomatically colonizes food-producing animals. In fact, >50% of U.S. swine production facilities test positive for Salmonella. The multidrug-resistant (MDR) Salmonella Typhimurium DT104 NCTC13348 c...

EpiReview: Typhoid fever, NSW, 2005-2011.

PubMed

Gunaratnam, Praveena; Tobin, Sean; Seale, Holly; Musto, Jennie

2013-11-01

To examine trends in the incidence of typhoid fever in NSW to inform the development of prevention strategies. Typhoid fever case notification data for the period 2005-2011 were extracted from the NSW Notifiable Conditions Information Management System. Population incidence rates were calculated and analysed by demographic variables. There were 250 case notifications of typhoid fever in NSW from 2005 to 2011, of which 240 are likely to have been acquired overseas. Case notifications remained relatively stable over the review period with the highest rates in Western Sydney Local Health District (10.9 per 100,000 population). Two-thirds (66.4%) of all case notifications are likely to have been acquired in South Asia, and about half of overseas-acquired case notifications were most likely to have been associated with travel to visit friends and relatives. Hospitalisation was required for 79.6% of cases where hospitalisation status was known. Prior typhoid vaccination was reported in 7% of cases in 2010 and 2011 where vaccination status was known. While typhoid fever rates remain low in NSW, case notifications of this preventable infection continue to be reported, particularly in travellers visiting friends and relatives in South Asia. Further research to better understand barriers to the use of preventive measures may be useful in targeting typhoid fever prevention messages in high-risk groups, particularly South Asian communities in NSW.

A TNF region haplotype offers protection from typhoid fever in Vietnamese patients

PubMed Central

2009-01-01

The genomic region surrounding the TNF locus on human chromosome 6 has previously been associated with typhoid fever in Vietnam. We used a haplotypic approach to understand this association further. Eighty single nucleotide polymorphisms (SNPs) spanning a 150 kb region were genotyped in 95 Vietnamese individuals (typhoid case/mother/father trios). A subset of data from 33 SNPs with a minor allele frequency of >4.3% was used to construct haplotypes. Fifteen SNPs, which tagged the 42 constructed haplotypes were selected. The haplotype tagging SNPs (T1-T15) were genotyped in 380 confirmed typhoid cases and 380 Vietnamese ethnically matched controls. Allelic frequencies of seven SNPs (T1, T2, T3, T5, T6, T7, T8) were significantly different between typhoid cases and controls. Logistic regression results support the hypothesis that there is just one signal associated with disease at this locus. Haplotype-based analysis of the tag SNPs provided positive evidence of association with typhoid (posterior probability 0.821). The analysis highlighted a low-risk cluster of haplotypes that each carry the minor allele of T1 or T7, but not both, and otherwise carry the combination of alleles *12122*1111 at T1-T11, further supporting the one associated signal hypothesis. Finally, individuals that carry the typhoid fever protective haplotype *12122*1111 also produce a relatively low TNF-α response to LPS. PMID:17503085

Vaccination against typhoid fever: present status.

PubMed Central

Ivanoff, B.; Levine, M. M.; Lambert, P. H.

1994-01-01

Typhoid fever remains an underestimated important health problem in many developing countries, causing more than 600,000 deaths annually in the world. Because of the reactogenicity of the parenteral, killed whole-cell vaccine, research has been oriented towards vaccination orally using live organisms and purified antigen. Live vaccine Ty21a, given by the oral route, has been extensively tested in several studies in developing countries. Its liquid formulation was the most effective, providing more than 60% protection after 7 years of follow-up. A Vi polysaccharide vaccine has been elaborated and provided more than 65% protection; after 3 years of follow-up the Vi antibody level was still at a high level. These two vaccines are therefore candidates for use in public health control programmes. Before such use, however, they need further evaluation for safety and protective efficacy when administered to the EPI-targeted age groups. The question of whether typhoid fever vaccines interfere with the response to simultaneously administered measles vaccine must also be studied. New live vaccines, given by the oral route in one dose, have been constructed through genetic engineering. The first results are promising, but they must be improved before use in a large-scale study. These strains could be used as live vector to deliver foreign antigens to the intestinal mucosa. PMID:7867143

9 CFR 145.94 - Terminology and classification; States.

Code of Federal Regulations, 2014 CFR

2014-01-01

... classification; States. (a) U.S. Pullorum-Typhoid Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with...)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have existed in...

9 CFR 145.94 - Terminology and classification; States.

Code of Federal Regulations, 2012 CFR

2012-01-01

... classification; States. (a) U.S. Pullorum-Typhoid Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with...)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have existed in...

9 CFR 145.94 - Terminology and classification; States.

Code of Federal Regulations, 2013 CFR

2013-01-01

... classification; States. (a) U.S. Pullorum-Typhoid Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with...)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have existed in...

Typhoid and dengue coinfection: case reports.

PubMed

Bansal, Rohit; Bansal, Priya; Tomar, Laxmikant Ramkumarsingh

2015-01-01

Both dengue and typhoid fever have emerged as major public health problems in India. Coinfection with both these diseases is rarely reported. Here we report two confirmed cases of concurrent illness of dengue with typhoid fever; both patients were managed as outpatients and recovered completely. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A review of typhoid fever transmission dynamic models and economic evaluations of vaccination.

PubMed

Watson, Conall H; Edmunds, W John

2015-06-19

Despite a recommendation by the World Health Organization (WHO) that typhoid vaccines be considered for the control of endemic disease and outbreaks, programmatic use remains limited. Transmission models and economic evaluation may be informative in decision making about vaccine programme introductions and their role alongside other control measures. A literature search found few typhoid transmission models or economic evaluations relative to analyses of other infectious diseases of similar or lower health burden. Modelling suggests vaccines alone are unlikely to eliminate endemic disease in the short to medium term without measures to reduce transmission from asymptomatic carriage. The single identified data-fitted transmission model of typhoid vaccination suggests vaccines can reduce disease burden substantially when introduced programmatically but that indirect protection depends on the relative contribution of carriage to transmission in a given setting. This is an important source of epidemiological uncertainty, alongside the extent and nature of natural immunity. Economic evaluations suggest that typhoid vaccination can be cost-saving to health services if incidence is extremely high and cost-effective in other high-incidence situations, when compared to WHO norms. Targeting vaccination to the highest incidence age-groups is likely to improve cost-effectiveness substantially. Economic perspective and vaccine costs substantially affect estimates, with disease incidence, case-fatality rates, and vaccine efficacy over time also important determinants of cost-effectiveness and sources of uncertainty. Static economic models may under-estimate benefits of typhoid vaccination by omitting indirect protection. Typhoid fever transmission models currently require per-setting epidemiological parameterisation to inform their use in economic evaluation, which may limit their generalisability. We found no economic evaluation based on transmission dynamic modelling, and no economic evaluation of typhoid vaccination against interventions such as improvements in sanitation or hygiene. Copyright © 2015. Published by Elsevier Ltd.

9 CFR 145.34 - Terminology and classification; States.

Code of Federal Regulations, 2012 CFR

2012-01-01

... classification; States. (a) U.S. Pullorum-Typhoid-Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with... § 145.93(b)(3)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have...

9 CFR 145.24 - Terminology and classification; States.

Code of Federal Regulations, 2014 CFR

2014-01-01

... classification; States. (a) U.S. Pullorum-Typhoid Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with... § 145.93(b)(3)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have...

9 CFR 145.34 - Terminology and classification; States.

Code of Federal Regulations, 2013 CFR

2013-01-01

... classification; States. (a) U.S. Pullorum-Typhoid-Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with... § 145.93(b)(3)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have...

9 CFR 145.24 - Terminology and classification; States.

Code of Federal Regulations, 2012 CFR

2012-01-01

... classification; States. (a) U.S. Pullorum-Typhoid Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with... § 145.93(b)(3)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have...

9 CFR 145.34 - Terminology and classification; States.

Code of Federal Regulations, 2014 CFR

2014-01-01

... classification; States. (a) U.S. Pullorum-Typhoid-Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with... § 145.93(b)(3)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have...

9 CFR 145.24 - Terminology and classification; States.

Code of Federal Regulations, 2013 CFR

2013-01-01

... classification; States. (a) U.S. Pullorum-Typhoid Clean State. (1) A State will be declared a U.S. Pullorum-Typhoid Clean State when it has been determined by the Service that: (i) The State is in compliance with... § 145.93(b)(3)(i) through (vii). (ii) No pullorum disease or fowl typhoid is known to exist nor to have...

[Sero-epidemiologic investigation on tick-borne diseases of humans and domestic animals in Zhejiang province].

PubMed

Chai, Cheng-liang; Lu, Qun-ying; Sun, Ji-min; Jiang, Li-ping; Ling, Feng; Zhang, Li-juan; Zheng, Shou-gui; Zhang, Hong; Ge, Jun-hua

2010-10-01

To investigate the seroprevalence of tick-borne diseases in humans and domestic animals from rural areas of Zhejiang province. Anji county, Jindong district and Tiantai county were selected for samples collection according to their geographic locations and historical prevalence of tick-borne diseases. Blood samples of humans and domestic animals were collected in the three sites. An indirect immuno-fluorescent antibody test was used to determine the presence of IgG antibodies of Rickettsiae heilongjiangii, Orientia tsutsugamushi, R. typhi, Anaplasma phagocytosis, Ehrlichia chaffeensis, Bartonella, R. hainan and Coxiella burnetii in these samples. Six hundred and eighty-three blood samples including 579 from humans and 104 from domestic animals (53 from cattles and 51 from sheep) were collected from the three sites. Antibody positive rates of Orientia tsutsugamushi, R. typhi, Ehrlichia chaffeensis and Coxiella burnetii were significantly different between these sites. IgG from all the 8 pathogens were detected in samples from humans. It was found that the sero-prevalence rates of R. typhi, Bartonella and C. burnetii (20.7%, 10.9%, 5.5%) of adults were higher than those of other Rickettsiae under investigation. The seroprevalence of R. typhi increased along with age. IgG from the 7 pathogens were detected in samples from domestic animals except for Anaplasma phagocytosis. The sero-prevalence rates of R. typhi, Bartonella and R. hainan (69.2%, 51.0%, 22.1%) of adults were higher than those of other Rickettsiae investigated. Tick-borne diseases did spread widely in humans and domestic animals from different rural areas of Zhejiang province. The sero-prevalence rates of R. typhi, B. henselae, R. hainan and C. burnetii were higher than that from other pathogens.

Salmonella typhi infection in a tertiary institution in Nasarawa State, Nigeria.

PubMed

Ishaleku, D; Sar, T T; Houmsou, R S

2011-02-01

To evaluate the prevalence of Sabmonella typhi (S.typhi) among subjects attending College of Education Health Clinic, Akwanga, Nasarawa state from the year. 2005 to 2007 and to recommend some preventive measures to the populace. Blood samples were tested for infection using the widal test. Out of the 793 patients examined, 579(73.0%) were positive with 174 (30.05%), 254(43.86%) and 151(26.07%) for the years 2005, 2006 and 2007 respectively. The age range with the highest prevalence of infection for the period was 21-30 with 207(35.75%) followed by 31-40 year group with 133 (22.97%). Chi-square analysis showed no significant difference in infection between males and females (P>0.05). The results of this study provide a useful guide in the formulation of S. typhi control measures in tertiary institutions in the State and also help to check the spread of the pathogen in the general population. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

RNA-seq analysis of prophage induction in multidrug-resistant salmonella enterica serovar typhimurium DT104 following exposure to the agricultural antibiotic carbadox

USDA-ARS?s Scientific Manuscript database

Non-typhoidal Salmonella is a leading cause of U.S. foodborne disease and food-related deaths. Multidrug-resistant (MDR) Salmonella Typhimurium DT104 contains 5 prophages in the genome that may be induced to produce phage under various environmental conditions, including antibiotic exposure. We inve...

Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study.

PubMed

Lo, Nathan C; Gupta, Ribhav; Stanaway, Jeffrey D; Garrett, Denise O; Bogoch, Isaac I; Luby, Stephen P; Andrews, Jason R

2018-02-12

Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective. We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year. Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness. Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

The Burden of Typhoid and Paratyphoid in India: Systematic Review and Meta-analysis

PubMed Central

Grassly, Nicholas C.

2016-01-01

Background Typhoid is an important public health challenge for India, especially with the spread of antimicrobial resistance. The decision about whether to introduce a public vaccination programme needs to be based on an understanding of disease burden and the age-groups and geographic areas at risk. Methods We searched Medline and Web of Science databases for studies reporting the incidence or prevalence of typhoid and paratyphoid fever confirmed by culture and/or serology, conducted in India and published between 1950 and 2015. We used binomial and Poisson mixed-effects meta-regression models to estimate prevalence and incidence from hospital and community studies, and to identify risk-factors. Results We identified 791 titles and abstracts, and included 37 studies of typhoid and 18 studies of paratyphoid in the systematic review and meta-analysis. The estimated prevalence of laboratory-confirmed typhoid and paratyphoid among individuals with fever across all hospital studies was 9.7% (95% CI: 5.7–16.0%) and 0.9% (0.5–1.7%) respectively. There was significant heterogeneity among studies (p-values<0.001). Typhoid was more likely to be detected among clinically suspected cases or during outbreaks and showed a significant decline in prevalence over time (odds ratio for each yearly increase in study date was 0.96 (0.92–0.99) in the multivariate meta-regression model). Paratyphoid did not show any trend over time and there was no clear association with risk-factors. Incidence of typhoid and paratyphoid was reported in 3 and 2 community cohort studies respectively (in Kolkata and Delhi, or Kolkata alone). Pooled estimates of incidence were 377 (178–801) and 105 (74–148) per 100,000 person years respectively, with significant heterogeneity between locations for typhoid (p<0.001). Children 2–4 years old had the highest incidence. Conclusions Typhoid remains a significant burden in India, particularly among young children, despite apparent declines in prevalence. Infant immunisation with newly-licensed conjugate vaccines could address this challenge. PMID:27082958

[Severe cases of Salmonella non typhi infections on sickle cell patients in Réunion Island].

PubMed

Vandroux, D; Jabot, J; Angue, M; Belcour, D; Galliot, R; Allyn, J; Gaüzère, B-A

2014-12-01

We report two cases of septic shocks due to Salmonella non typhi infection on sickle cell patients admitted to an intensive care unit. Such patients should enforce food hygiene measures, especially under tropical settings, to avoid potentially deadly severe infections.

Medical Surveillance Monthly Report. Volume 21, Number 6

DTIC Science & Technology

2014-06-01

presentations of diarrhea and vomiting (e.g., botulism, brucellosis, hep- atitis A, trichinosis, and typhoid fever ). For the purposes of this report...norovirus, salmonellosis, shigellosis, trichinosis, and typhoid fever . Informa- tion on GI outbreaks that occurred dur- ing the surveillance period, but... Typhoid fever 8 5 1 . 2 Listeriosis 4 1 1 1 1 Cholera 3 3 . . . Vibrio parahaemolyticus 3 2 . 1 . Trichinosis 3 1 1 1 . Botulism 2 . 2 . . Cyclospora

Typhoid fever acquired in the United States, 1999–2010: epidemiology, microbiology, and use of a space–time scan statistic for outbreak detection

PubMed Central

IMANISHI, M.; NEWTON, A. E.; VIEIRA, A. R.; GONZALEZ-AVILES, G.; KENDALL SCOTT, M. E.; MANIKONDA, K.; MAXWELL, T. N.; HALPIN, J. L.; FREEMAN, M. M.; MEDALLA, F.; AYERS, T. L.; DERADO, G.; MAHON, B. E.; MINTZ, E. D.

2016-01-01

SUMMARY Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space–time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space–time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space–time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection. PMID:25427666

Social and Economic Burden Associated With Typhoid Fever in Kathmandu and Surrounding Areas: A Qualitative Study.

PubMed

Kaljee, Linda M; Pach, Alfred; Garrett, Denise; Bajracharya, Deepak; Karki, Kshitu; Khan, Imran

2017-07-29

Typhoid fever is a significant contributor to infectious disease mortality and morbidity in low- and middle-income countries, particularly in South Asia. With increasing antimicrobial resistance, commonly used treatments are less effective and risks increase for complications and hospitalizations. During an episode of typhoid fever, households experience multiple social and economic costs that are often undocumented. In the current study, qualitative interview data from Kathmandu and surrounding areas provide important insights into the challenges that affect those who contract typhoid fever and their caregivers, families, and communities, as well as insight into prevention and treatment options for health providers and outreach workers. When considering typhoid fever cases confirmed by blood culture, our data reveal delays in healthcare access, financial and time costs burden on households, and the need to increase health literacy. These data also illustrate the impact of limited laboratory diagnostic equipment and tools on healthcare providers' abilities to distinguish typhoid fever from other febrile conditions and treatment challenges associated with antimicrobial resistance. In light of these findings, there is an urgent need to identify and implement effective preventive measures including vaccination policies and programs focused on at-risk populations and endemic regions such as Nepal. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Typhoid fever acquired in the United States, 1999-2010: epidemiology, microbiology, and use of a space-time scan statistic for outbreak detection.

PubMed

Imanishi, M; Newton, A E; Vieira, A R; Gonzalez-Aviles, G; Kendall Scott, M E; Manikonda, K; Maxwell, T N; Halpin, J L; Freeman, M M; Medalla, F; Ayers, T L; Derado, G; Mahon, B E; Mintz, E D

2015-08-01

Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space-time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space-time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space-time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.

Typhoid fever: hurdles to adequate hand washing for disease prevention among the population of a peri-urban informal settlement in Fiji.

PubMed

Greenwell, James; McCool, Judith; Kool, Jacob; Salusalu, Mosese

2013-01-01

The Pacific island nation of Fiji Islands has high rates of endemic typhoid fever which is difficult to diagnose and often underreported. However, the majority of cases are preventable through use of safe water; adequate sanitation; vaccination; and, most sustainable of all, simple hygienic behaviour, such as hand washing with soap (HWWS). Despite many attempts by public health authorities, little progress has been made in the area of environmental adaptation and behaviour change. To explore perceptions of typhoid fever risk among urban squatters and behavioural determinants surrounding HWWS, indigenous Fijians living in informal settlements with high typhoid fever incidence were invited to participate in focus group discussions. In-depth interviews were conducted with community leaders. Perceptions of typhoid fever suggest confusion about risk factors, symptoms and communicability. Environmental barriers for hand washing were related to water and soap access. Standard social marketing approaches have been trialled with little clear evidence of impact. Despite this, we continue to advocate for the social and cultural determinants of typhoid prevention to remain central to future public health strategies. Despite behaviour change being notoriously difficult, we argue that community-driven behaviour adaptation initiatives based on sound epidemiological evidence and health communication theory are likely to have significant impact and greater likelihood of sustainability.

Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment.

PubMed

Mogasale, Vittal; Maskery, Brian; Ochiai, R Leon; Lee, Jung Seok; Mogasale, Vijayalaxmi V; Ramani, Enusa; Kim, Young Eun; Park, Jin Kyung; Wierzba, Thomas F

2014-10-01

No access to safe water is an important risk factor for typhoid fever, yet risk-level heterogeneity is unaccounted for in previous global burden estimates. Since WHO has recommended risk-based use of typhoid polysaccharide vaccine, we revisited the burden of typhoid fever in low-income and middle-income countries (LMICs) after adjusting for water-related risk. We estimated the typhoid disease burden from studies done in LMICs based on blood-culture-confirmed incidence rates applied to the 2010 population, after correcting for operational issues related to surveillance, limitations of diagnostic tests, and water-related risk. We derived incidence estimates, correction factors, and mortality estimates from systematic literature reviews. We did scenario analyses for risk factors, diagnostic sensitivity, and case fatality rates, accounting for the uncertainty in these estimates and we compared them with previous disease burden estimates. The estimated number of typhoid fever cases in LMICs in 2010 after adjusting for water-related risk was 11·9 million (95% CI 9·9-14·7) cases with 129 000 (75 000-208 000) deaths. By comparison, the estimated risk-unadjusted burden was 20·6 million (17·5-24·2) cases and 223 000 (131 000-344 000) deaths. Scenario analyses indicated that the risk-factor adjustment and updated diagnostic test correction factor derived from systematic literature reviews were the drivers of differences between the current estimate and past estimates. The risk-adjusted typhoid fever burden estimate was more conservative than previous estimates. However, by distinguishing the risk differences, it will allow assessment of the effect at the population level and will facilitate cost-effectiveness calculations for risk-based vaccination strategies for future typhoid conjugate vaccine. Copyright © 2014 Mogasale et al. Open Access article distributed under the terms of CC BY-NC-SA. Published by .. All rights reserved.

Field Trial of Attenuated Salmonella typhi Live Oral Vaccine Ty21a in Liquid and Enteric-Coated Formulations and Epidemiological Survey for Incidence of Diarrhea Due to Shigella Species

DTIC Science & Technology

1992-04-30

8217 diarrhea in Mexico . A prospective study of physicians and family members attending a congress. N Eng J Med 1976; 294:1299-1305. 14 18. Black RE...Schoolnik GK, Riley LW. Diffuse-adhering Escherichia coli (DAEC) as a putatuve cause of diarrhea in Mayan children in mexico . J Infect Dis 1991; 164...diarrhea and show that Shi- land village in Guatemala (3), and a village geIla has a propensity to cause severe diar- in Mexico (12). Only the rural

[Some information regarding the historical development of typhoid fever in Chile].

PubMed

Laval, Enrique

2017-10-01

During the historical development of typhoid fever in Chile, its confusion with other infectious diseases is particularly noteworthy, especially with murine typhus, a problem that was mainly resolved during the 1918 epidemic. The importance of chloramphenicol treatment is also highlighted, which meant an enormous improvement in typhoid/paratyphoid fevers, in combination with public health and health education actions that allowed to almost eliminate these infectious diseases in our country.

Severe thrombocytopenia in a child with typhoid fever: a case report.

PubMed

Al Reesi, Mohammed; Stephens, Glenn; McMullan, Brendan

2016-11-30

Although thrombocytopenia is common in typhoid fever, its course, response to treatment, and need for specific therapies such as platelet transfusion are not well characterized. We report a case of typhoid fever in a 4-year-old Asian male returned traveler, admitted with prolonged fever and found to have severe thrombocytopenia (platelets 16 × 10 9 /L). Despite appropriate antibiotic therapy, his platelet recovery was slow, but did not lead to complications and he did not require platelet transfusion. There is no consensus in the medical literature guiding the optimal management of severe thrombocytopenia in typhoid fever, but it may improve with conservative management, as in our case. The epidemiology and management of this condition merits further research to guide clinical practice.

[A case of Salmonella paratyphi A infection in Poland].

PubMed

Sobczyk-Krupiarz, Iwona; Garlicki, Aleksander; Biesiada, Grazyna; Czepiel, Jacek; Skwara, Paweł; Salamon, Dominika; Mach, Tomasz

2008-01-01

Paratyphoid fever is an acute infection caused by Salmonella paratyphi A, B or C. The disease is transmitted from person to person by fecal-oral way. Typical for typhoid fever are splenomegaly, bradycardia, fever, constipation or mild diarrhoea oftten associated with abdominal tenderness. We present the case of patient who was infected by Salmonella paratyphi C while his travelling in Asia.